797 results on '"Acute monocytic leukemia"'
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2. Venetoclax and Azacitidine Combined With Chidamide (VAC) for the Treatment of Newly Diagnosed Acute Monocytic Leukemia
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Jining Medical University, The Second People's Hospital of Huai'an, First Affiliated Hospital Bengbu Medical College, Northern Jiangsu People's Hospital, Affiliated Hospital of Nantong University, Suzhou Hospital of Traditional Chinese Medicine, Taizhou University, and Sheng-Li Xue, MD, Principal Investigator
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- 2023
3. Leukemia cutis simulating drug reaction with eosinophilia and systemic symptoms following beta-lactam antibiotic use
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Jaclyn Abraham, BS, Navid Farahbakhsh, MD, and Kiran Motaparthi, MD
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acute monocytic leukemia ,acute myeloid leukemia ,antibiotics ,DRESS ,drug reaction ,leukemia cutis ,Dermatology ,RL1-803 - Published
- 2024
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4. Melatonin Enhances the Effect of ABT-737 in Acute Monocytic Leukemia THP-1 Cells.
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Lomovsky, A. I., Baburina, Y. L., Fadeev, R. S., Kobyakova, M. I., Lomovskaya, Ya. V., Krestinin, R. R., Sotnikova, L. D., and Krestinina, O. V.
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CELL death , *ACUTE leukemia , *MELATONIN , *PINEAL gland , *MEMBRANE potential , *ENDOPLASMIC reticulum - Abstract
Melatonin (N-acetyl-5-methoxytryptamine, MEL) is a hormone synthesized by the pineal gland. Due to its oncostatic effect, it can be considered as an antitumor agent and used for combination therapy. ABT-737, a Bcl-2 inhibitor, promotes cell death after treatment with agents that induce pro-apoptotic signals. In the present study, the combined effect of MEL and ABT-737 on changes in proliferative and mitotic activity, mitochondrial membrane potential, intracellular production of reactive oxygen species (ROS), and cytosolic Ca2+ was studied. Moreover, changes in the expression of anti- and pro-apoptotic proteins (Bcl-2 and Bax), autophagy markers (LC3A/B (I, II)), endoplasmic reticulum stress markers (chaperones BIP and PDI, CHOP) were studied under these conditions. The effect of MEL together with ABT-737 led to an increase in the level of cytosolic Ca2+, intracellular production of ROS and a decrease in the membrane potential of mitochondria. The content of Bcl-2 increased, while the level of Bax decreased. Activation of CHOP stimulated autophagy and led to a decrease in the synthesis of chaperones BIP and PDI. It is assumed that melatonin can enhance the effect of other chemotherapeutic agents and can be used in the treatment of tumors. [ABSTRACT FROM AUTHOR]
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- 2024
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5. The evaluation of the anti-cancer effects of Anoectochilus roxburghii on hematological cancers in vitro.
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Gunes, Buket Altinok, Ozkan, Tulin, Gonulkirmaz, Nurbanu, and Sunguroglu, Asuman
- Abstract
The cause of hematological cancers is the uncontrolled proliferation of hematopoietic and lymphoid tissues, and chemotherapy is used to treat cancer. However, adverse side effects of chemotherapy are common. Therefore, the use of plant extracts as a method for treating cancer is becoming increasingly popular. Anoectochilus roxburghii (wall.) Lindl. (A. roxburghii) is one of the original sources of the valuable medicinal plants known as the king medicine and the golden grass. This study investigated the potential anticancer effect of A. roxburghi (AR) on JURKAT, MM1S, THP1 and U266 cells. To test the cytotoxic and apoptotic effects of AR, hematological cancer cells were exposed to increasing doses of AR (0.1–0.5 µg/µl). The spectrophotometric MTT assay and the flow cytometric Annexin V staining were used to examine the viability and apoptosis of the cells, respectively. qRT-PCR was used to determine the expression levels of the apoptosis-related genes BAD, BAX, BIM and BCL-2. Our results show that AR treatment decreased cell viability and induced apoptosis in each cell line. Our RT-PCR data showed that AR significantly increased the expression levels of the pro-apoptotic BAX gene in JURKAT and MM1S cells, whereas it significantly increased the expression levels of both BAX and BIM in U266 cells. This is the first study to investigate how AR modulates apoptosis in hematological cancer cells. As a result, AR therapy may be a promising treatment modality for the treatment of cancer. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Acute monocytic leukemia with KMT2A::LASP1 developed 9 months after diagnosis of acute megakaryoblastic leukemia in a 2-year-old boy.
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Fujita, Takashi, Fukushima, Hiroko, Nanmoku, Toru, Arakawa, Yuki, Deguchi, Takao, Suzuki, Ryoko, Yamaki, Yuni, Hosaka, Sho, and Takada, Hidetoshi
- Abstract
Acute myeloid leukemia (AML) is known as one of the subsequent malignant neoplasms that can develop after cancer treatment, but it is difficult to distinguish from relapse when the preceding cancer is leukemia. We report a 2-year-old boy who developed acute megakaryoblastic leukemia (AMKL, French-American-British classification [FAB]: M7) at 18 months of age and achieved complete remission with multi-agent chemotherapy without hematopoietic stem cell transplantation. Nine months after diagnosis and 4 months after completing treatment for AMKL, he developed acute monocytic leukemia (AMoL) with the KMT2A::LASP1 chimeric gene (FAB: M5b). The second complete remission was achieved using multi-agent chemotherapy and he underwent cord blood transplantation 4 months after AMoL was diagnosed. He is currently alive and disease free at 39 and 48 months since his AMoL and AMKL diagnoses, respectively. Retrospective analysis revealed that the KMT2A::LASP1 chimeric gene was detected 4 months after diagnosis of AMKL. Common somatic mutations were not detected in AMKL or AMoL and no germline pathogenic variants were detected. Since the patient's AMoL was different from his primary leukemia of AMKL in terms of morphological, genomic, and molecular analysis, we concluded that he developed a subsequent leukemia rather than a relapse of his primary leukemia. [ABSTRACT FROM AUTHOR]
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- 2023
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7. A RARE CASE OF ACUTE MYELOID LEUKEMIA WITH CENTRAL NERVOUS SYSTEM INVOLVEMENT.
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Vazar-Tripon, Daiana-Andreea, Muntean, Maria-Miruna, Filimon, Robert-Alexandru, and Jimbu, Ioana-Laura
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SKULL radiography , *CEREBROSPINAL fluid examination , *ADRENOCORTICAL hormones , *IDARUBICIN , *IMMUNOPHENOTYPING , *SPINAL injections , *HEMIPLEGIA , *MENINGITIS , *COMPUTED tomography , *METHOTREXATE , *CENTRAL nervous system , *TREATMENT effectiveness , *CONFERENCES & conventions , *CYTARABINE , *ETOPOSIDE , *DISEASE complications ,BONE marrow examination - Abstract
Introduction: Acute myeloid leukemia is characterized by the proliferation of immature cells, called blasts, and it is frequently associated with an ineffective hematopoiesis. Extramedullary disease, such as central nervous sistem involvent, granulocytic sarcoma or leukemia cutis is rare. The nucleophosmin 1(NPM1) gene is one of the most commonly mutated genes in AML and it is associated with a favorable prognosis. Case Report: A 73-year-old female was admitted in December 2023 to the hematology department presenting marked leukocytosis with monocytosis, thrombocytopenia and mild anemia. The peripheral blood smear showed 64% blasts. A bone marrow aspiration and immunophenotying was performed which confirmed the diagnosis of acute monoblastic leukemia. Molecular biology showed no mutations in FMS-like tyrosine kinase 3 (FLT3) ITD or TKD genes but a mutation in the NPM1 gene was positive. Caryotying was not available, due to national holidays. Due the marked leukocytosis, cytoreductive treatment with hydroxyurea was initiated. On the same day, the patient presented acute respiratory failure and fever and she was transferred to the intensive care unit department. A head and chest CT scan revealed cortico-subcortical atrophy and signs of pulmonary infection for which antibiotherapy and antifungal therapy was initiated. After a few days the patients was transferred to back the hematology department where azacitidine, a hypomethylating agent and venetoclax, a BCL-2 inhibitor (B-cell lymphoma 2) was initiated. After one cycle the complete blood count was almost normalized but the patient complained about a generalized, erythematous, slightly itchy rash. A skin biopsy was performed and was positive for leukemia cutis. In February 2024, the patient presented with left hemiparesis. A CSF (cerebrospinal fluid) smear and skull CT were performed, which indicated the presence of blastic meningitis. Intrathecal administration of methotrexate, cytarabine and corticosteroids failed to improve the neurological symptoms. A second line treatment with etoposide and idarubicine was started but the patient died within weeks. Discussions : SNC involvent in AML is an uncommon phenomena. The presence of both skin and SNC involvement, simultaneous, suggests a very agreessive disease. Conclusions: AML with mutated NPM1 is ussualy associated with a favorable prognosis. However, in this case the disease was very aggresssive. Despite advancements in therapeutic regimens, the prognosis remains very poor in the elderly population. [ABSTRACT FROM AUTHOR]
- Published
- 2024
8. Therapy-Related Acute Myeloid Leukemia Mimicking Lymphoma: a Diagnostic Dilemma.
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Juanjuan Zhang, Nan Wang, Ying Guo, Huijuan Song, and Jing Xu
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ACUTE myeloid leukemia ,LYMPHOMAS ,MYELODYSPLASTIC syndromes ,MYELOPROLIFERATIVE neoplasms ,ACUTE leukemia ,PROGRESSION-free survival ,RITUXIMAB - Abstract
Background: Based on the 2017 revision of the World Health Organization Classification, therapy-related myeloid neoplasms consist of therapy-related acute myeloid leukemia, therapy-related myelodysplastic syndromes, and therapy-related myelodysplastic/myeloproliferative neoplasms, which exist as a late-occurring complication of radiation and/or chemotherapy treatment due to previous application of iatrogenic mutagenic agents. Methods: Here we present the first described case of therapy-related acute monocytic leukemia mimicking lymphoma after chemotherapy and radiotherapy for breast cancer. Results: Based on immunophenotypic analysis and biopsy of the BM, the patient was diagnosed with acute monocytic leukemia (AML FAB M5b) according to WHO classification. Due to short interval of development, a diagnosis of therapy-related acute monocytic leukemia was made. Conclusions: The atypical morphology of the patient, a diagnostic mistake, resulted in an initial diagnosis of secondary lymphoma. Recognizing the atypical morphology is vital in distinguishing it from lymphoma, which is closely related to the treatment and prognosis of the patient. [ABSTRACT FROM AUTHOR]
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- 2022
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9. A case of rhinocerebral mucormycosis with brain abscess drained by endoscopic endonasal skull base surgery
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Kensuke Uraguchi, Kenichi Kozakura, Satoshi Oka, Takaya Higaki, Seiichiro Makihara, Toshi Imai, Akira Doi, Tsuyoshi Ohta, Shin Kariya, and Kazunori Nishizaki
- Subjects
Rhinocerebral mucormycosis ,Acute rhinosinusitis ,Brain abscess ,Endoscopic endonasal skull base surgery ,Acute monocytic leukemia ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
A 70-year-old Japanese man undergoing remission induction therapy for acute monocytic leukemia (AML-M5b) developed fever and headache, and was started on antibiotics and liposomal amphotericin B (L-AMB). There was no improvement, and computed tomography and contrast-enhanced magnetic resonance imaging revealed acute rhinosinusitis and brain abscess. Successful endoscopic endonasal surgery was performed at this point, providing drainage for the rhinosinusitis and abscess. Histopathological findings showed the mucormycosis.
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- 2020
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10. Prognostic stratification of molecularly and clinically distinct subgroup in children with acute monocytic leukemia
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Li‐Peng Liu, Ao‐Li Zhang, Min Ruan, Li‐Xian Chang, Fang Liu, Xia Chen, Ben‐Quan Qi, Li Zhang, Yao Zou, Yu‐Mei Chen, Xiao‐Juan Chen, Wen‐Yu Yang, Ye Guo, and Xiao‐Fan Zhu
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acute monocytic leukemia ,children ,clinical characteristics ,gene mutation ,prognostic factors ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The prognosis of children with acute monocytic leukemia (AML‐M5) remains unsatisfactory and the risk profile is still controversial. We aim to investigate the prognostic value of clinical and cytogenetic features and propose a new risk stratification in AML‐M5 children. Methods We included 132 children with AML‐M5. Overall survival (OS) and progression‐free survival (PFS) were documented. Cox regression was performed to evaluate the potential risk factors of prognosis. Results The 5‐year‐OS was 46.0% (95% confidence intervals, 41.6%‐50.4%) in all patients. There was significantly lower OS in the age ≤ 3 years old (P = .009) and hyperleukocytosis (P
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- 2020
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11. Leukemia cutis simulating drug reaction with eosinophilia and systemic symptoms following beta-lactam antibiotic use.
- Author
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Abraham J, Farahbakhsh N, and Motaparthi K
- Abstract
Competing Interests: None disclosed.
- Published
- 2024
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12. Oral Mucosal Lesions of Systemic Diseases
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Jin, Xin, Zeng, Xin, Wu, Lanyan, Chen, Qianming, editor, and Zeng, Xin, editor
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- 2018
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13. Reports from Institute of Theoretical & Experimental Biophysics Add New Data to Findings in Acute Monocytic Leukemia (Melatonin Enhances the Effect of Abt-737 In Acute Monocytic Leukemia Thp-1 Cells).
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ACUTE leukemia ,BIOPHYSICS ,MELATONIN ,FREE radical scavengers - Abstract
A recent study conducted in Moscow Oblast, Russia, has explored the potential of melatonin as an antitumor agent in the treatment of Acute Monocytic Leukemia (AML). The study investigated the combined effect of melatonin and ABT-737, a Bcl-2 inhibitor, on various cellular processes and protein expression in AML cells. The results showed that the combination of melatonin and ABT-737 led to increased cytosolic calcium levels, reactive oxygen species production, and decreased mitochondrial membrane potential. Additionally, the study found changes in the expression of anti- and pro-apoptotic proteins, autophagy markers, and endoplasmic reticulum stress markers. The researchers concluded that melatonin may enhance the effect of other chemotherapeutic agents and could be used in tumor treatment. [Extracted from the article]
- Published
- 2024
14. Research Results from Taipei Medical University Update Understanding of Acute Monocytic Leukemia (Ribonucleic Acid Sequencing Reveals the Upregulation and Resolution of Inflammation and Extracellular Matrix Remodeling in Lidocaine-Treated Human...).
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ACUTE leukemia ,EXTRACELLULAR matrix ,RNA ,CARDIOVASCULAR agents ,INFLAMMATION - Abstract
A recent report from Taipei Medical University discusses the potential role of lidocaine, a local anesthetic commonly used in dentistry, in modulating the immune system and reducing inflammation. The study aimed to investigate how lidocaine influences cell behavior using RNA sequencing. The results showed that high doses of lidocaine had a cytotoxic effect on THP-1 cells, but lower doses induced an anti-inflammatory profile by upregulating tissue remodeling and resolving inflammation. The study suggests that lidocaine may have therapeutic effectiveness in dental tissue repair. [Extracted from the article]
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- 2024
15. Solasonine Suppresses the Proliferation of Acute Monocytic Leukemia Through the Activation of the AMPK/FOXO3A Axis
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Hong Zhang, Fang Tian, Pengjun Jiang, Shushu Qian, Xingbin Dai, Bangyun Ma, Mengya Wang, Huibo Dai, Xiaocao Sha, Zhongfa Yang, Xuejun Zhu, and Xuemei Sun
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solasonine ,Solanum nigrum L. ,acute monocytic leukemia ,AMPK ,FOXO3A ,AMPK/FOXO3A ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Solasonine, the main active ingredient of Solanum nigrum L., has been reported to exert extensive antitumor activity. However, the antitumor effects in acute monocytic leukemia and the exact mechanisms involved are unknown. In this study, we investigated the role of solasonine on inhibiting the progression of acute monocytic leukemia. Our findings showed that solasonine inhibited the proliferation of acute monocytic leukemic cell lines (THP-1 and MV4-11) in vitro. Solasonine promoted apoptosis and induced cell cycle arrest in the G2/M phase. Analysis of RNA-seq data suggested that solasonine correlated with increased expression of genes in the AMPK/FOXO3A pathway. Inhibition of AMPK with compound C followed by treatment with solasonine showed that solasonine reduced apoptosis, caused less cell cycle arrest, and inactivated the AMPK/FOXO3A axis in THP-1 and MV4-11 cells. Solasonine also inhibited tumor growth by the activation of the AMPK/FOXO3A axis. In conclusion, solasonine inhibited the progress of acute monocytic leukemia in vitro and in vivo and triggered the apoptosis and cell cycle arrest in the G2/M phase by upregulating the AMPK/FOXO3A pathway.
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- 2021
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16. HEMOPHAGOCYTOSIS BY BLASTS IN A CHILD WITH ACUTE MONOCYTIC LEUKEMIA AFTER CHEMOTHERAPY.
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Granero Farias, Mariela, Correa Freitas, Priscila Aparecida, Spagnol, Fabiane, Viquetti de Souza, Meriene, Paula Alegretti, Ana, Riegel, Mariluce, Rodrigues Taniguchi, Adriano Nori, and Esteves Daudt, Liane
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ACUTE leukemia , *MACROPHAGE activation syndrome , *HEMOPHAGOCYTIC lymphohistiocytosis , *BONE marrow , *CANCER chemotherapy , *KARYOTYPES - Abstract
Objective: To describe the case of a child who presented hemophagocytic lymphohistiocytosis (HLH) associated with acute monocytic leukemia after chemotherapy, with hemophagocytosis caused by leukemic cells. Case description: In a university hospital in Southern Brazil, a 3-yearold female was diagnosed with acute monocytic leukemia with normal karyotype. The chemotherapy regimen was initiated, and she achieved complete remission six months later, relapsing after four months with a complex karyotype involving chromosomes 8p and 16q. The bone marrow showed vacuolated blasts with a monocytic aspect and evidence of hemophagocytosis. The child presented progressive clinical deterioration and died two months after the relapse. Comments: HLH is a rare and aggressive inflammatory condition characterized by cytopenias, hepatosplenomegaly, fever, and hemophagocytosis in the bone marrow, lymph nodes, spleen, and liver. Although rare, malignancy-associated HLH (M-HLH) is fatal. The patient in this case report met five out of the eight established criteria for HLH. The evolution of the patient’s karyotype, regardless of the diagnostic profile, seemed secondary to the treatment for acute monocytic leukemia. In this case, the cytogenetic instability might have influenced the abnormal behavior of leukemic cells. This is a rare case of HLH in a child with acute monocytic leukemia. [ABSTRACT FROM AUTHOR]
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- 2021
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17. Decades Long Involvement of THP-1 Cells as a Model for Macrophage Research: A Comprehensive Review.
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Sharma P, Venkatachalam K, and Binesh A
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- Humans, THP-1 Cells, Immunity, Innate, Macrophages immunology
- Abstract
Over the years, researchers have endeavored to identify dependable and reproducible in vitro models for examining macrophage behavior under controlled conditions. The THP-1 cell line has become a significant and widely employed tool in macrophage research within these models. Originating from the peripheral blood of individuals with acute monocytic leukemia, this human monocytic cell line can undergo transformation into macrophage-like cells, closely mirroring primary human macrophages when exposed to stimulants. Macrophages play a vital role in the innate immune system, actively regulating inflammation, responding to infections, and maintaining tissue homeostasis. A comprehensive understanding of macrophage biology and function is crucial for gaining insights into immunological responses, tissue healing, and the pathogenesis of diseases such as viral infections, autoimmune disorders, and neoplastic conditions. This review aims to thoroughly evaluate and emphasize the extensive history of THP-1 cells as a model for macrophage research. Additionally, it will delve into the significance of THP-1 cells in advancing our comprehension of macrophage biology and their invaluable contributions to diverse scientific domains., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2024
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18. A case of rhinocerebral mucormycosis with brain abscess drained by endoscopic endonasal skull base surgery.
- Author
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Uraguchi, Kensuke, Kozakura, Kenichi, Oka, Satoshi, Higaki, Takaya, Makihara, Seiichiro, Imai, Toshi, Doi, Akira, Ohta, Tsuyoshi, Kariya, Shin, and Nishizaki, Kazunori
- Abstract
A 70-year-old Japanese man undergoing remission induction therapy for acute monocytic leukemia (AML-M5b) developed fever and headache, and was started on antibiotics and liposomal amphotericin B (L-AMB). There was no improvement, and computed tomography and contrast-enhanced magnetic resonance imaging revealed acute rhinosinusitis and brain abscess. Successful endoscopic endonasal surgery was performed at this point, providing drainage for the rhinosinusitis and abscess. Histopathological findings showed the mucormycosis. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
19. HEMOPHAGOCYTOSIS BY BLASTS IN A CHILD WITH ACUTE MONOCYTIC LEUKEMIA AFTER CHEMOTHERAPY
- Author
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Mariela Granero Farias, Priscila Aparecida Correa Freitas, Fabiane Spagnol, Meriene Viquetti de Souza, Ana Paula Alegretti, Mariluce Riegel, Adriano Nori Rodrigues Taniguchi, and Liane Esteves Daudt
- Subjects
Acute monocytic leukemia ,Hemophagocytic lymphohistiocytosis ,Hemophagocytic syndrome ,Macrophage activation syndrome ,Pediatrics ,RJ1-570 - Abstract
ABSTRACT Objective: To describe the case of a child who presented hemophagocytic lymphohistiocytosis (HLH) associated with acute monocytic leukemia after chemotherapy, with hemophagocytosis caused by leukemic cells. Case description: In a university hospital in Southern Brazil, a 3-year-old female was diagnosed with acute monocytic leukemia with normal karyotype. The chemotherapy regimen was initiated, and she achieved complete remission six months later, relapsing after four months with a complex karyotype involving chromosomes 8p and 16q. The bone marrow showed vacuolated blasts with a monocytic aspect and evidence of hemophagocytosis. The child presented progressive clinical deterioration and died two months after the relapse. Comments: HLH is a rare and aggressive inflammatory condition characterized by cytopenias, hepatosplenomegaly, fever, and hemophagocytosis in the bone marrow, lymph nodes, spleen, and liver. Although rare, malignancy-associated HLH (M-HLH) is fatal. The patient in this case report met five out of the eight established criteria for HLH. The evolution of the patient’s karyotype, regardless of the diagnostic profile, seemed secondary to the treatment for acute monocytic leukemia. In this case, the cytogenetic instability might have influenced the abnormal behavior of leukemic cells. This is a rare case of HLH in a child with acute monocytic leukemia.
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- 2020
- Full Text
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20. JAK2-negative acute monocytic leukemia with TET2 mutation in essential thrombocythemia with JAK2 mutation with literature review
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Toshie Ogasawara, Kiyotaka Kawauchi, Takuya Ono, Shoko Marshall, Kotaro Shide, Kazuya Shimoda, Naoki Mori, and Hiroshi Sakura
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Essential thrombocythemia ,Acute monocytic leukemia ,Myeloproliferative neoplasm ,10–11 Translocation 2 protein ,Janus activating kinase 2 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Essential thrombocythemia (ET) is an indolent myeloproliferative neoplasm (MPN) with a transformation to acute myeloid leukemia in
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- 2020
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21. Haemophagocytic lymphohistiocytosis occurred during induction chemotherapy in an acute monocytic leukemia patient with FLT3-ITD and DNMT3A mutations
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Fei Li, Xiaojie Zhang, Yunyun Wang, Ailin Yang, Zhanglin Zhang, Weiping Tang, Nan Zhong, and Huidong Shi
- Subjects
Haemophagocytic lymphohistiocytosis ,Malignancy ,Acute monocytic leukemia ,FLT3-ITD ,DNMT3A ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Haemophagocytic lymphohistiocytosis (HLH) is considered to be a large challenge for clinicians due to the variable overlaps of symptoms with other severe diseases and a high rate of mortality. Prompt diagnosis and treatment are crucial to avoid a fatal outcome. However, very limited reports have focused on HLH during chemotherapy (Ch-HLH) due to a low incidence and insufficient knowledge. Case presentation A 22-year-old male was diagnosed with acute monocytic leukemia with FLT3-ITD and DNMT3A mutations and pulmonary infection. He received IA regimen (Idarubicin, 8 mg/m2/d for 3 days and cytarabine, 100 mg/m2/d for 7 days) chemotherapy, anti-infection drugs and blood components transfusions. During the stage of bone marrow suppression, he presented with a fever, cytopenia (WBC, 0.43 × 109/L; Hb, 73 g/L and PLT, 1 × 109/L), refractory coagulation dysfunction (APTT, 104.0 s; PT, 30.5 s and Fbg, 0.87 g/L), splenomegaly (3 cm below the costal margin), hyperferritinemia (SF > 3000 μg/L), increased soluble interleukin-II receptors (sIL-2R > 7500 u/mL) and haemophagocytosis in the bone marrow and was diagnosed with HLH. After he was treated with methylprednisolone at 500 mg/d for 3 days, 120 mg/d for 3 days and 80 mg/d for 3 days, followed by a gradually reduced dose combined with powerful anti-infection drugs, his symptoms subsided and his abnormal parameters recovered to normal levels. Conclusion Patients with HLH in acute leukemia have a high rate of mortality. This case report provides helpful clinical experiences relative to the recognition and treatment of Ch-HLH for clinicians.
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- 2018
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22. PFKFB4 is critical for the survival of acute monocytic leukemia cells.
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Wang, Gongai, Li, Shumei, Xue, Kewei, and Dong, Shasha
- Subjects
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ACUTE leukemia , *ACUTE myeloid leukemia , *APOPTOSIS , *GENE fusion , *CELLS - Abstract
Acute myeloid leukemia (AML), which is characterized by an overproliferation of blood cells, is divided into several subtypes in adults and children. Of those subtypes, acute monocytic leukemia (M4/M5, AMoL) is reported to be associated with abnormal gene fusions that result in monocytic cell differentiation being blocked. However, few studies have shown a relationship between cellular metabolism and the initiation of AMoL. Here, we use the open-access database TCGA to analyze the expression of enzymes in the metabolic cycle and find that PFKFB4 is highly expressed in AMoL. Subsequently, knocking down PFKFB4 in THP-1 and U937 cells significantly inhibits cell growth and increases the sensitivity of cells to chemical drug-induced apoptosis. In line with the gene-editing alterations, treatment with a PFKFB4 inhibitor exhibits similar effects on THP-1 and U937 proliferation and apoptosis. In addition, we find that PFKFB4 functions as a reliable target of the epigenetic regulator MLL, which is a well-known modulator in AMoL. Mechanistically, MLL promotes PFKFB4 expression at the transcriptional level through the putative E2F6 binding site in the promoter of the pfkfb4 gene. Taken together, our results suggest PFKFB4 serves as a downstream target of MLL and functions as a potent therapeutic target in AMoL. • PFKFB4 level is associated with prognosis for acute monocytic leukemia. • PFKFB4 inhibitor effectively suppresses AMoL cells growth. • Knockdown of PFKFB4 increases the sensitivity of AMoL cells to drug-induced apoptosis. • MLL regulates PFKFB4 expression at the transcriptional level. [ABSTRACT FROM AUTHOR]
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- 2020
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23. Prognostic stratification of molecularly and clinically distinct subgroup in children with acute monocytic leukemia.
- Author
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Liu, Li‐Peng, Zhang, Ao‐Li, Ruan, Min, Chang, Li‐Xian, Liu, Fang, Chen, Xia, Qi, Ben‐Quan, Zhang, Li, Zou, Yao, Chen, Yu‐Mei, Chen, Xiao‐Juan, Yang, Wen‐Yu, Guo, Ye, and Zhu, Xiao‐Fan
- Subjects
- *
ACUTE leukemia , *STEM cell transplantation , *HEMATOPOIETIC stem cells , *PROTEIN-tyrosine kinases , *PROGRESSION-free survival - Abstract
Background: The prognosis of children with acute monocytic leukemia (AML‐M5) remains unsatisfactory and the risk profile is still controversial. We aim to investigate the prognostic value of clinical and cytogenetic features and propose a new risk stratification in AML‐M5 children. Methods: We included 132 children with AML‐M5. Overall survival (OS) and progression‐free survival (PFS) were documented. Cox regression was performed to evaluate the potential risk factors of prognosis. Results: The 5‐year‐OS was 46.0% (95% confidence intervals, 41.6%‐50.4%) in all patients. There was significantly lower OS in the age ≤ 3 years old (P =.009) and hyperleukocytosis (P <.001). The FMS‐like tyrosine kinase 3 (FLT3)‐internal tandem duplication (ITD) and MLL‐rearrangement carriers were associated with fewer survivors in all patients (37.1% and 36.7%) and chemotherapy‐only group (19.0% and 35.0%). Notably, the number of survivor with MLL‐rearrangement did not increase in hematopoietic stem cell transplant (HSCT) group. According to the Cox regression analysis, HSCT was a significantly favorable factor (P =.001), while hyperleukocytosis, age ≤ 3 years old, and BM blast ≥ 70% adversely affected the OS in all patients (all P <.05). Additionally, FLT3‐ITD was a risk factor for OS in the chemotherapy‐only group (P =.023), while hyperleukocytosis and age ≤ 3 years independently contributed to poor PFS (both P <.05). In comparison to the standard‐risk group, significant poorer outcome was found in the high‐risk group (both P <.005). Conclusions: We propose that AML‐M5 children with any of MLL‐rearrangement, FLT3‐ITD, hyperleukocytosis, BM blast ≥ 70%, or age ≤ 3 years old are classified into the high‐risk group, and HSCT is beneficial especially in patients with FLT3‐ITD mutation, hyperleukocytosis, and age ≤ 3 years old. Importantly, the choice of HSCT should be made more carefully in children with MLL‐rearrangement for its suboptimal performance. [ABSTRACT FROM AUTHOR]
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- 2020
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24. Establishment and characterization of a DOT1L inhibitor-sensitive human acute monocytic leukemia cell line YBT-5 with a novel KMT2A-MLLT3 fusion.
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Wang, Zhenhua, Shi, Yongjin, Liu, Huihui, Liang, Zeyin, Zhu, Qiang, Wang, Lihong, Tang, Bo, Miao, Shengchao, Ma, Ning, Cen, Xinan, Ren, Hanyun, and Dong, Yujun
- Subjects
ACUTE leukemia ,CELL lines ,GRANULOCYTE-macrophage colony-stimulating factor ,MYELOID leukemia ,SODIUM fluoride ,ANIMAL experimentation ,ANTINEOPLASTIC agents ,BIOLOGICAL models ,BONE marrow ,DRUG resistance in cancer cells ,IMMUNOPHENOTYPING ,KARYOTYPES ,MICE ,POLYMERASE chain reaction ,PROTEINS ,RESEARCH funding ,TRANSFERASES ,FLUORESCENCE in situ hybridization ,ACUTE myeloid leukemia ,NUCLEAR proteins ,PHARMACODYNAMICS - Abstract
Immortalized cell lines are useful for deciphering the pathogenesis of acute leukemia and developing novel therapeutic agents against this malignancy. In this study, a new human myeloid leukemia cell line YBT-5 was established. After more than 1-year cultivation from the bone marrow of a patient with acute monocytic leukemia, YBT cell line was established. Then a subclone, YBT-5, was isolated from YBT using single cell sorting. Morphological and cytogenetical characterizations of the YBT-5 cell line were determined by cytochemical staining, flow cytometry analysis, and karyotype analysis. Molecular features were identified by transcriptomic analysis and reverse transcription-polymerase chain reaction. To establish a tumor model, 5 × 106 YBT-5 cells were injected subcutaneously in nonobese diabetic/severe combined immune-deficiency (NOD/SCID) mice. DOT1L has been proposed as a potential therapeutic target for KMT2A-related leukemia; therefore, to explore the potential application of this new cell line, its sensitivity to a specific DOT1L inhibitor, EPZ004777 was measured ex vivo. The growth of YBT-5 does not depend on granulocyte-macrophage colony-stimulating factor. Cytochemical staining showed that α-naphthyl acetate esterase staining was positive and partially inhibited by sodium fluoride, while peroxidase staining was negative. Flow cytometry analysis of YBT-5 cells showed positive myeloid and monocytic markers. Karyotype analysis of YBT-5 showed 48,XY,+8,+8. The breakpoints between KMT2A exon 10 and exon 11 (KMT2A exon 10/11) and MLLT3 exon 5 and exon 6 (MLLT3 exon 5/6) were identified, which was different from all known breakpoint locations, and a novel fusion transcript KMT2A exon 10/MLLT3 exon 6 was formed. A tumor model was established successfully in NOD/SCID mice. EPZ004777 could inhibit the proliferation and induce the differentiation of YBT-5 cells. Therefore, a new acute monocytic leukemia cell line with clear biological and molecular features was established and may be used in the research and development of new agents targeting KMT2A-associated leukemia. [ABSTRACT FROM AUTHOR]
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- 2019
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25. The expression of fibronectin is significantly suppressed in macrophages to exert a protective effect against Staphylococcus aureus infection
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Hong-Yi Chen, Mei-Hui Lin, Chien-Cheng Chen, and Jwu-Ching Shu
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HepG2 Cell ,Focal Adhesion Kinase ,Crystal Violet Staining ,Acute Monocytic Leukemia ,Overnight Bacterial Culture ,Microbiology ,QR1-502 - Abstract
Abstract Background Fibronectin (Fn) plays a major role in the attachment of Staphylococcus aureus to host cells by bridging staphylococcal fibronectin-binding proteins (FnBPs) and cell-surface integrins. A previous study demonstrated that the phagocytosis of S. aureus by macrophages is enhanced in the presence of exogenous Fn. We recently found that FnBPs overexpression also enhances phagocytic activity. The effect of S. aureus infection on the expression of macrophage Fn was investigated. Result The level of Fn secreted by monocytes (THP-1), macrophages, human lung adenocarcinoma (A549) cells, and hepatocellular carcinoma (HepG2) cells in response to S. aureus infection was determined by Western blotting and it was significantly suppressed only in macrophages. The activation of signaling pathways associated with Fn regulation in macrophages and HepG2 cells was also investigated by Western blotting. Erk was activated in both macrophages and HepG2 cells, whereas Src-JNK-c-Jun signaling was only activated in macrophages. A significant decrease in macrophage viability was observed in response to S. aureus infection in the presence of exogenous Fn. Conclusion The Src-JNK-c-Jun signaling pathway was activated in macrophages in response to S. aureus infection and resulted in the suppression of Fn expression. This suppression may play a protective role in macrophages against S. aureus infection. This study provides the first demonstration that Fn is suppressed in macrophages by S. aureus infection.
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- 2017
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26. The evaluation of the anti-cancer effects of Anoectochilus roxburghii on hematological cancers in vitro.
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Gunes BA, Ozkan T, Gonulkirmaz N, and Sunguroglu A
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- Humans, bcl-2-Associated X Protein, Apoptosis, Cell Line, Tumor, Neoplasms, Antineoplastic Agents pharmacology, Hematologic Neoplasms drug therapy
- Abstract
The cause of hematological cancers is the uncontrolled proliferation of hematopoietic and lymphoid tissues, and chemotherapy is used to treat cancer. However, adverse side effects of chemotherapy are common. Therefore, the use of plant extracts as a method for treating cancer is becoming increasingly popular. Anoectochilus roxburghii (wall.) Lindl. (A. roxburghii) is one of the original sources of the valuable medicinal plants known as the king medicine and the golden grass. This study investigated the potential anticancer effect of A. roxburghi (AR) on JURKAT, MM1S, THP1 and U266 cells. To test the cytotoxic and apoptotic effects of AR, hematological cancer cells were exposed to increasing doses of AR (0.1-0.5 µg/µl). The spectrophotometric MTT assay and the flow cytometric Annexin V staining were used to examine the viability and apoptosis of the cells, respectively. qRT-PCR was used to determine the expression levels of the apoptosis-related genes BAD, BAX, BIM and BCL-2. Our results show that AR treatment decreased cell viability and induced apoptosis in each cell line. Our RT-PCR data showed that AR significantly increased the expression levels of the pro-apoptotic BAX gene in JURKAT and MM1S cells, whereas it significantly increased the expression levels of both BAX and BIM in U266 cells. This is the first study to investigate how AR modulates apoptosis in hematological cancer cells. As a result, AR therapy may be a promising treatment modality for the treatment of cancer., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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27. Cytogenetics and associated mutation profile in patients with acute monocytic leukemia.
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Xing, Shanshan, Wang, Biao, Gao, Yu, Li, Mengjie, Wang, Tong, Sun, Yiwu, Shen, Yimin, and Chao, Hongying
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ACUTE myeloid leukemia diagnosis , *CYTOGENETICS , *KARYOTYPES , *MOLECULAR diagnosis , *GENETIC mutation , *RESEARCH funding , *GENETIC testing , *GENE rearrangement , *DESCRIPTIVE statistics , *SEQUENCE analysis - Abstract
Introduction: Cytogenetics and molecular testings for disease classifying and prognosis estimation are becoming routine in clinical practice. However, the molecular characteristics of acute monocytic leukemia (AML‐M5) remain unclear. The aim of this study was to investigate the association between karyotypes and gene mutations, especially in AML‐M5 patients with 11q23/KMT2A (MLL) rearrangement and normal karyotype. Methods: A total of 126 de novo AML‐M5 patients were screened for mutations in the 51 genes known or suspected to have a role in myeloid malignancies or in monocytic differentiation using next‐generation sequencing (NGS). Chromosome karyotype analysis was performed by R‐banding method and further confirmed either by fluorescence in situ hybridization (FISH) and/or by multiple reverse transcription polymerase chain reaction (multiple RT‐PCR). Results: Of the 126 patients, one or more mutations were detected in 83.3% patients. FLT3‐ITD and NRAS had the highest mutation frequency, followed by NPM1, DNMT3A, TET2, KRAS, and RUNX1. We also identified a significant difference in mutational spectrums between KMT2A‐rearranged (KMT2Ar) patients and normal karyotype (NK) patients, as reflected in the average number of gene mutations per patient (1.66 vs 2.46), and in the frequencies of commonly mutated genes (FLT3‐ITD: 6% vs 43.5%; NPM1: 0% vs 43.5%; RUNX1: 2.0% vs 15.2%; DNMT3A: 4% vs 26.1%; KRAS: 24.0% vs 4.35%). Patients harboring ≥3 mutations showed much lower complete remission rate than that with double mutations (P = 0.043) in high‐risk group. Conclusion: There was a significantly different mutation profile between KMT2Ar‐patients and NK patients. Our research provided new insight into the molecular characteristics of AML‐M5. [ABSTRACT FROM AUTHOR]
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- 2019
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28. Priming with GM-CSF instead of G-CSF enhances CAG-induced apoptosis of acute monocytic leukemia cells in vitro.
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Lei, Meiqing, Liu, Limin, and Wu, Depei
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ACUTE leukemia , *GRANULOCYTE-macrophage colony-stimulating factor , *ACUTE myeloid leukemia , *APOPTOSIS , *RESEARCH , *RESEARCH methodology , *EVALUATION research , *MEDICAL cooperation , *COMPARATIVE studies , *RESEARCH funding , *CELL lines - Abstract
High expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor has been found in myelomonocytic or monocytic subtypes (M4/M5) of acute myeloid leukemia. Herein, we aimed to improve the effect of CAG [Ara-C, ACR, and G-CSF (granulocyte colony-stimulating factor)] regimen for acute monocytic leukemia by replacing G-CSF with GM-CSF. Results showed that the percentage of cells in S phase was higher with GM-CSF than with G-CSF treatment at 20 ng/mL (P < 0.05). When THP-1 and SHI-1 cells were primed with 20 ng/mL G-CSF or GM-CSF followed by Ara-C and ACR, cell proliferation rate in the CAGM (Ara-C, ACR, and GM-CSF) regimen was lower than in the CAG regimen (P < 0.05). Furthermore, CAGM regimen induced more obvious cell apoptosis than CAG regimen probably by reducing Bcl-2/Bax ratio (P < 0.05). Similar results were seen in primary cells from M5 patients. Collectively, our study suggests that priming with GM-CSF may be more effective than G-CSF in CAG regimen in acute monocytic leukemia. [ABSTRACT FROM AUTHOR]
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- 2019
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29. Overexpression of miR-21 is involved in acute monocytic leukemia-associated angiogenesis by targeting IL-12.
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He, Xue-Peng, Chen, Peng, Yang, Kai, Liu, Bing, Zhang, Yuan, Wang, Fang, Guo, Zhi, Liu, Xiao-Dong, Lou, Jin-Xing, and Chen, Hui-Ren
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- *
NEOVASCULARIZATION , *MICRORNA , *VASCULAR endothelial growth factors , *MONOCYTIC leukemia , *INTERLEUKIN-12 - Abstract
Angiogenesis is important in pathophysiological processes, including the pathogenesis of acute monocytic leukemia (AML). MicroRNA-21 (miR-21) is overexpressed and exhibits oncogenic activity in cancer. However, the biological mechanism underlying the effect of miR-21 in AML remains to be fully elucidated. In the present study, the expression levels of miR-21 and vascular endothelial growth factor (VEGF) were determined in 26 patients with AML and 28 healthy individuals. The secretion of VEGF was also measured following the transfection of THP-1 cells with miR-21 mimic or inhibitor. The supernatants of the THP-1 cells, which were transfected with miR-21 mimic, inhibitor or small interfering RNA (si)VEGF, respectively, were used to incubate human umbilical vein endothelial cells (HUVECs), following which tube formation of the HUVECs was measured. miR-21 targets were predicted using a biological target prediction website and confirmed using a luciferase assay. The effects of interleukin (IL)-12 were investigated by examining the tube formation of HUVECs and the secretion of VEGF following recombinant human (rh) IL-12 pretreatment. The results revealed that miR-21 and VEGF expression was significantly increased in the peripheral blood monocytes of the patients, compared with the healthy controls. There was negative correlation between the expression of IL-12 and miR-21 in the serum of patients with AML. Furthermore, supernatant VEGF levels from the miR-21 mimic-transfected THP-1 cells were increased, whereas a decreasing trend was observed in the miR-21 inhibitor group. The angiogenic ability of the HUVECs pretreated with supernatant from the THP-1 cells transfected with miR-21 mimic was higher, and was lower in THP-1 cells co-transfected with miR-21 mimic and siVEGF, compared with the miR-21 mimic only group. A luciferase assay demonstrated that IL-12 was the direct target of miR-21, and the level of IL-12 in the supernatant of THP-1 cells transfected with miR-21 mimic was increased. IL-12 pretreatment increased VEGF expression and angiogenic ability in HUVECs. The inactivation of miR-21 or activation of its target gene may be a potential therapeutic strategy in human AML. [ABSTRACT FROM AUTHOR]
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- 2018
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30. Researcher from Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology Reports on Findings in Acute Monocytic Leukemia (Influence of Microbiota-Related Metabolites Associated with Inflammation and Sepsis on the...).
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ACUTE leukemia ,CRITICAL care medicine ,RESEARCH personnel ,METABOLITES ,MICROBIAL metabolites - Abstract
A recent study conducted by researchers from the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology in Moscow, Russia, explored the role of microbiota-related metabolites in acute monocytic leukemia. The study focused on the influence of these metabolites on the activity of cyclooxygenase (COX), an enzyme involved in inflammation. The researchers found that certain metabolites, such as phenylpropionic acid and itaconic acid, inhibited the activity of COX. These findings suggest that microbial metabolites may play a role in regulating COX activity and could have implications for the development of treatments for leukemia and other inflammatory conditions. [Extracted from the article]
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- 2023
31. β-Carboline Glucoalkaloids from Psychotria cupularis and Evaluation of Their Antileishmanial Activity
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Paulo Otávio Lourenço Moreira, Daniela Nabak Bueno Maia, Tânia M. A. Alves, Djalma Menezes de Oliveira, Ivan Martins Barreto, Guadalupe Edilma Licona de Macedo, and Betania Barros Cota
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Indole test ,Rubiaceae ,biology ,Traditional medicine ,Chemistry ,Monoterpene ,medicine.disease ,biology.organism_classification ,Leishmania ,Ethanol extracts ,parasitic diseases ,medicine ,Psychotria ,Acute monocytic leukemia ,General Pharmacology, Toxicology and Pharmaceutics ,IC50 - Abstract
Purification of the crude ethanol extracts from leaves and stems of Psychotria cupularis (Mull.Arg.) Standl., Rubiaceae, resulted in the isolation of the known monoterpene indole alkaloids ophiorine B and lyalosidic and strictosidinic acids. The antileishmanial activity values found for the isolated compounds highlighted ophiorine B as the most active against Leishmania (Viannia) braziliensis (IC50 100.50 μg/ml or 196.1 μM) and Leishmania (Leishmania) amazonensis (IC50 3.69 μg/ml or 7.2 μM) with a selectivity index of 108.6 to the human acute monocytic leukemia THP-1 cells. To the best of our knowledge, this is the first time that antileishmanial β-carboline glucoalkaloids were isolated from the studied material plant, contributing to the pharmacological potential of the genus.
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- 2021
32. Anti-Leukemic Properties of Histamine in Monocytic Leukemia: The Role of NOX2
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Roberta Kiffin, Hanna Grauers Wiktorin, Malin S. Nilsson, Johan Aurelius, Ebru Aydin, Brianna Lenox, Jonas A. Nilsson, Anders Ståhlberg, Fredrik B. Thorén, Kristoffer Hellstrand, and Anna Martner
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histamine ,NAPDH oxidase ,NOX2 ,acute myeloid leukemia ,acute monocytic leukemia ,acute myelomonocytic leukemia ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
In patients with acute myeloid leukemia (AML), treatment with histamine dihydrochloride (HDC) and low-dose IL-2 (HDC/IL-2) in the post-chemotherapy phase has been shown to reduce the incidence of leukemic relapse. The clinical benefit of HDC/IL-2 is pronounced in monocytic forms of AML, where the leukemic cells express histamine type 2 receptors (H2R) and the NAPDH oxidase-2 (NOX2). HDC ligates to H2Rs to inhibit NOX2-derived formation of reactive oxygen species, but details regarding the anti-leukemic actions of HDC remain to be elucidated. Here, we report that human NOX2+ myelomonocytic/monocytic AML cell lines showed increased expression of maturation markers along with reduced leukemic cell proliferation after exposure to HDC in vitro. These effects of HDC were absent in corresponding leukemic cells genetically depleted of NOX2 (NOX2−/−). We also observed that exposure to HDC altered the expression of genes involved in differentiation and cell cycle progression in AML cells and that these effects required the presence of NOX2. HDC promoted the differentiation also of primary monocytic, but not non-monocytic, AML cells in vitro. In a xenograft model, immunodeficient NOG mice were inoculated with wild-type or NOX2−/− human monocytic AML cells and treated with HDC in vivo. The administration of HDC reduced the in vivo expansion of NOX2+/+, but not of NOX2−/− human monocytic AML cells. We propose that NOX2 may be a conceivable target in the treatment of monocytic AML.
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- 2018
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33. The effect of Kagocel® on gene expression of Toll-like receptors of innate immunity in THP-1 human monocytes with different levels of differentiation
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T. M. Sokolova and V. V. Poloskov
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differentiation of thp-1 monocytes ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Acute monocytic leukemia ,Receptor ,innate immunity ,030304 developmental biology ,0303 health sciences ,Innate immune system ,Chemistry ,TLR9 ,medicine.disease ,kagocel® preparation ,Molecular biology ,TLR2 ,Cell culture ,tlr ,030220 oncology & carcinogenesis ,Monocyte differentiation ,Automotive Engineering ,TLR4 ,gene expression ,Medicine ,TP248.13-248.65 ,Biotechnology - Abstract
Kagocel® is used in Russia for the treatment of viral infections. In terms of its chemical structure, Kagocel® active ingredient is a copolymer of gossypol polyphenol and carboxymethylcellulose. The study investigated antiviral and cytokine-inducing activity of Kagocel®, as well as its toxic effects. The aim of the study was to investigate the effect of Kagoce ® active ingredient on the induction of expression of the innate immune system receptor genes (Toll-like receptors, TLR) in the THP-1 human acute monocytic leukemia cell line with different levels of differentiation. Materials and methods: the effect of Kagocel active ingredient was investigated at the concentrations of 0.2 and 2 mg/mL in the THP-1 human acute monocytic leukemia cell line with different levels of differentiation: non-differentiated monocytes, and monocytes differentiated into macrophage-like cells. Comparative analysis of the activity of TLR 2, 3, 4, 7, 8, 9 genes was carried out by quantitative RT-PCR. The study determined standard deviations of the levels of gene expression in the experimental cells (2deltaCq ± SD) relative to the expression in the control cells. Results: Kagocel active ingredient at the concentration of 0.2 mg/mL induced activation of TLR2 expression in THP-1 monocytes by 3.5 times, TLR3 by 2 times, TLR4 by 1.6 times, and at the concentration of 2 mg/mL also induced activation of TLR7 and TLR8 by 1.4 times, and TLR9 by 2 times. The levels of TLR2, TLR3, TLR9 induction were significantly higher in THP-1 monocytes partially differentiated into macrophage-like cells, and the highest stimulation level was observed for TLR2 (8 times). Conclusions: the results obtained characterise Kagocel® as a stimulator of TLR genes in the THP-1 cell line. The number of TLR genes induced in THP-1 monocytes was shown to increase with the increase in the product concentration. THP-1 monocyte differentiation into macrophage-like cells enhances susceptibility to Kagocel®. The positive regulation of TLR genes activity may account for antiviral and interferon-inducing properties of Kagocel®, and also suggests the possibility of expanding the use of the product for various immune-associated diseases.
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- 2021
34. Acute Myeloid Leukemia with Myelodysplasia-Related Changes and Therapy-Related Acute Myeloid Leukemia
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Konoplev, Sergej N., Bueso-Ramos, Carlos E., and Dunphy, Cherie H., editor
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- 2010
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35. 下调MLAA-22基因对U937细胞增殖与分化的影响.
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崔 鹤 and 张王刚
- Abstract
Objective To explore the effect of down-regulation of MLAA-22 gene on proliferation and differentiation of U937 cells. Methods MLAA-22 gene was down-regulated by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system in U937 cells. The activity of single guide RNA (sgRNA) was detected by Cruiser™ enzyme digestion assay. The mutation rate of MLAA-22 gene was analyzed by TA cloning and sequencing assay of PCR products of the gene mutation region. Cell proliferation was evaluated by CCK-8 assay. Expression of CD11b was tested by flow cytometry to evaluate cell differentiation. Results Cruiser™ enzyme digestion assay showed the sgRNA of the CRISPR/Cas9 system identified the target spot efficiently. TA cloning and sequencing assay displayed the mutation rate of MLAA-22 gene was 61.3%. CCK-8 assay demonstrated that the proliferation was obviously inhibited in MLAA-22-knockdown U937 cells. In addition, flow cytometry assay indicated CD11b-positive cells significantly increased in MLAA-22-knockdown U937 cells. Conclusion MLAA-22 gene regulates the proliferation of U937 cells probably by regulating their differentiation, thus promoting the occurrence and development of acute monocytic leukemia. [ABSTRACT FROM AUTHOR]
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- 2018
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36. Anti-Leukemic Properties of Histamine in Monocytic Leukemia: The Role of NOX2.
- Author
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Kiffin, Roberta, Grauers Wiktorin, Hanna, Nilsson, Malin S., Aurelius, Johan, Aydin, Ebru, Lenox, Brianna, Nilsson, Jonas A., Ståhlberg, Anders, Thorén, Fredrik B., Hellstrand, Kristoffer, and Martner, Anna
- Subjects
DRUG efficacy ,ACUTE myeloid leukemia treatment ,ANTINEOPLASTIC agents - Abstract
In patients with acute myeloid leukemia (AML), treatment with histamine dihydrochloride (HDC) and low-dose IL-2 (HDC/IL-2) in the post-chemotherapy phase has been shown to reduce the incidence of leukemic relapse. The clinical benefit of HDC/IL-2 is pronounced in monocytic forms of AML, where the leukemic cells express histamine type 2 receptors (H
2 R) and the NAPDH oxidase-2 (NOX2). HDC ligates to H2 Rs to inhibit NOX2-derived formation of reactive oxygen species, but details regarding the anti-leukemic actions of HDC remain to be elucidated. Here, we report that human NOX2+ myelomonocytic/monocytic AML cell lines showed increased expression of maturation markers along with reduced leukemic cell proliferation after exposure to HDCin vitro . These effects of HDC were absent in corresponding leukemic cells genetically depleted of NOX2 (NOX2 −/− ). We also observed that exposure to HDC altered the expression of genes involved in differentiation and cell cycle progression in AML cells and that these effects required the presence of NOX2. HDC promoted the differentiation also of primary monocytic, but not non-monocytic, AML cellsin vitro . In a xenograft model, immunodeficient NOG mice were inoculated with wild-type orNOX2 −/− human monocytic AML cells and treated with HDCin vivo . The administration of HDC reduced thein vivo expansion ofNOX2 +/+ , but not ofNOX2 −/− human monocytic AML cells. We propose that NOX2 may be a conceivable target in the treatment of monocytic AML. [ABSTRACT FROM AUTHOR]- Published
- 2018
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37. Haemophagocytic lymphohistiocytosis occurred during induction chemotherapy in an acute monocytic leukemia patient with FLT3-ITD and DNMT3A mutations.
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Li, Fei, Zhang, Xiaojie, Wang, Yunyun, Yang, Ailin, Zhang, Zhanglin, Tang, Weiping, Zhong, Nan, and Shi, Huidong
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CYTARABINE , *MALES , *DISEASES , *ANTI-infective agents , *ANTINEOPLASTIC agents , *BONE marrow , *GENOMES , *GENETIC mutation , *RESEARCH funding , *HEMOPHAGOCYTIC lymphohistiocytosis , *TRANSFERASES , *ACUTE myeloid leukemia , *TREATMENT effectiveness , *METHYLPREDNISOLONE - Abstract
Background: Haemophagocytic lymphohistiocytosis (HLH) is considered to be a large challenge for clinicians due to the variable overlaps of symptoms with other severe diseases and a high rate of mortality. Prompt diagnosis and treatment are crucial to avoid a fatal outcome. However, very limited reports have focused on HLH during chemotherapy (Ch-HLH) due to a low incidence and insufficient knowledge.Case Presentation: A 22-year-old male was diagnosed with acute monocytic leukemia with FLT3-ITD and DNMT3A mutations and pulmonary infection. He received IA regimen (Idarubicin, 8 mg/m2/d for 3 days and cytarabine, 100 mg/m2/d for 7 days) chemotherapy, anti-infection drugs and blood components transfusions. During the stage of bone marrow suppression, he presented with a fever, cytopenia (WBC, 0.43 × 109/L; Hb, 73 g/L and PLT, 1 × 109/L), refractory coagulation dysfunction (APTT, 104.0 s; PT, 30.5 s and Fbg, 0.87 g/L), splenomegaly (3 cm below the costal margin), hyperferritinemia (SF > 3000 μg/L), increased soluble interleukin-II receptors (sIL-2R > 7500 u/mL) and haemophagocytosis in the bone marrow and was diagnosed with HLH. After he was treated with methylprednisolone at 500 mg/d for 3 days, 120 mg/d for 3 days and 80 mg/d for 3 days, followed by a gradually reduced dose combined with powerful anti-infection drugs, his symptoms subsided and his abnormal parameters recovered to normal levels.Conclusion: Patients with HLH in acute leukemia have a high rate of mortality. This case report provides helpful clinical experiences relative to the recognition and treatment of Ch-HLH for clinicians. [ABSTRACT FROM AUTHOR]- Published
- 2018
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38. STAT3 信号通路在人急性单核细胞白血病细胞向树突状细胞分化中的作用及机制探讨
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施引, 朱肖肖, 张振, 郭强, 赵霖, 魏然, 孙琳琳, 尹训强, 张云虹, 姜国胜, and 李霞
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TRANSDUCERS , *MONOCYTIC leukemia , *DENDRITIC cells , *GRANULOCYTE antigens , *PHOSPHORYLATION kinetics , *GENETICS , *PHYSIOLOGY - Abstract
Objective To detect the role and mechanisms of signal transducers and activators of transcription 3(STAT3) in promoting the differentiation of human acute monocytic leukemia eells into dendritic cells(DCs). Methods Human acute monocytic leukemia cells THP-1 were randomly divided into two groups: the observation group and the control group. Cells in the observation group were induced to differentiate into DCs by granulocyte-macrophage colony stimulating factor (GM-CSF) combined with interleukin-4 (IL-4), and we used Lipopolysaccharide (LPS) to induce THP-1-derived DC maturation; cells in the control group were not treated. The cells in the two groups were collected on day 7 of culture, the morphologic features were observed under inverted microscope; DC surface marker CDlle and DC surface functional molecules(CD80, HLA-DR, and CCR7) were detected by flow cytometry; the mRNA expression of STAT3 and E2-2 was detected by q-PCR; in addition, the protein expression of STAT3 and phosphorylation (p-STAT3) was detected by Western blotting. Results The cells in the control group showed a round shape and uniform morphology. After cytokines induction, obvious morphological changes of DCs were observed. Compared with the control group, the DC surface marker CD11c and DC surface functional molecules of the observation group were higher, and both the mRNA expression levels of STAT3 and E2-2 and the protein expression levels of STAT3 and p-STAT3 increased signifieandy (all Pc 0.05). Conclusion During the differentiation of THP-1 cells into DCs induced by GM-CSF and IL-4 , STAT3 signaling pathway activates specific nuclear transcription factor E2-2 , which in turn induces the differentiation of THP-1 into DCs. [ABSTRACT FROM AUTHOR]
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- 2018
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39. Dihydroartemisinin‑induced apoptosis in human acute monocytic leukemia cells.
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Cao, Jia-Tian, Mo, Hui-Min, Wang, Yue, Zhao, Kai, Zhang, Tian-Tian, Wang, Chang-Qian, Xu, Kai-Lin, and Han, Zhi-Hua
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LEUKEMIA treatment , *ARTEMISININ derivatives , *GENE expression , *APOPTOSIS , *CANCER cells ,LEUKEMIA genetics - Abstract
Dihydroartemisinin (DHA) is a derivative of artemisinin. The present study aimed to investigate whether DHA induces apoptosis in the THP‑1 human acute monocytic leukemia cell line (AMoL), and to identify the relative molecular mechanisms. The results of the present study demonstrated that the viability of THP‑1 cells were inhibited by DHA in a dose‑ and time‑dependent manner, which was accompanied by morphological characteristics associated with apoptosis. After 24 h of 200 μM DHA treatment, the proportion of apoptotic cells was significantly increased compared with the untreated controls (P<0.01). In addition, DHA downregulated the levels of B‑cell lymphoma (Bcl)‑2, protein kinase B (Akt)1, Akt2 and Akt3 gene expression, and increased the expression of the Bcl‑2‑associated X protein apoptosis regulator. The protein expression of phospho‑Akt and phospho‑extracellular signal‑regulated kinase (ERK) was also decreased, and the protein expression level of cleaved caspase‑3 was increased following treatment with DHA. Therefore, DHA may induce apoptosis in the AMoL THP‑1 cell line via currently unknown underlying molecular mechanisms, including the downregulation of ERK and Akt, and the activation of caspase‑3. [ABSTRACT FROM AUTHOR]
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- 2018
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40. Virosecurinine induces apoptosis in human leukemia THP-1 cells and other underlying molecular mechanisms.
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Zhang, Gang, Gao, Xiaohui, Zeng, Hui, Li, Yuan, and Guo, Xiaojun
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MONOCYTIC leukemia , *CELL proliferation , *PROPIDIUM iodide , *ANTINEOPLASTIC agents , *CELL cycle - Abstract
Virosecurinine, a primary alkaloid from Securinega suffruticosa plant is known as a potent differentiation- inducing agent in acute leukemia cells. The present study aimed to investigate the effects and underlying mechanisms of virosecurinine on human leukemia THP-1 cells in vitro. The effects of virosecurinine on cell proliferation were assessed by CCK-8. The effects on apoptosis and cell cycle were assessed by staining with annexin V-fluorescein isothiocyanate and propidium iodide, respectively followed by flow cytometric analysis. The apoptotic cell bodies were observed using a transmission electron microscope, while the mRNA expression of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), mechanistic target of rapamycin (mTOR) and phosphatase and tensin homolog (PTEN) in THP-1 was evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Treatment with virosecurinine was able to decrease the viability of THP-1 cells in a dose- and time-dependent manner. The IC50 values of virosecurinine at 24, 48, and 72 h post-treatment were 68.128, 23.615, and 13.423 µmol/l, respectively. Cell cycle was arrested at the G1/S phase in virosecurinine-treated cells; however, not in untreated control cells. Numerous apoptotic bodies were observed in the THP-1 cells, which were treated with 12.5 µmol/l virosecurinine for 48 h. RT-qPCR indicated that treatment with virosecurinine resulted in upregulated PTEN expression and downregulated expression of PI3K, AKT and mTOR in THP-1 cells. The present study demonstrated that treatment with virosecurinine was able to inhibit proliferation and induce apoptosis in THP-1cells by exerting an inhibitory effect on the activation of PI3K/AKT/mTOR signaling pathways. Therefore, our data suggested that virosecurinine is a promising anti-tumor agent for the treatment of acute monocytic leukemia. [ABSTRACT FROM AUTHOR]
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- 2018
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41. Leukemic gingival enlargement: A case report and review of literature.
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Chowdhri, Kanika, Tandon, Shruti, Lamba, Arundeep Kaur, and Faraz, Farrukh
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GINGIVAL hyperplasia ,MONOCYTIC leukemia ,IMMUNOPHENOTYPING ,ACUTE myeloid leukemia ,MORTALITY ,DIAGNOSIS - Abstract
The oral cavity manifests signs of various systemic diseases. This entails thorough examination of the oral mucosa, gingiva, teeth, tongue and other oral tissues. Occasionally, oral signs can be an expression of systemic conditions such as endocrine imbalance, nutritional deficiencies and blood disorders. Leukemia is a malignancy of white blood cells, which may result in significant morbidity and mortality. Oral changes maybe the first and only presenting features in leukemia patients, making it imperative for the dentist to diagnose the disease accurately. [ABSTRACT FROM AUTHOR]
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- 2018
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42. First Clinical Medical College of Lanzhou University Researchers Have Provided New Study Findings on Acute Monocytic Leukemia (Invasive splenic mucormycosis due to Rhizopus microsporus during chemotherapy for acute monocytic leukemia: a case...).
- Abstract
Acute Monocytic Leukemia, Cancer, Chemotherapy, Drugs and Therapies, Fungal Diseases and Conditions, Health and Medicine, Hematology, Leukemia, Monocytic Leukemia, Mucormycosis, Mycoses, Oncology, Zygomycosis Keywords: Acute Monocytic Leukemia; Cancer; Chemotherapy; Drugs and Therapies; Fungal Diseases and Conditions; Health and Medicine; Hematology; Leukemia; Monocytic Leukemia; Mucormycosis; Mycoses; Oncology; Zygomycosis EN Acute Monocytic Leukemia Cancer Chemotherapy Drugs and Therapies Fungal Diseases and Conditions Health and Medicine Hematology Leukemia Monocytic Leukemia Mucormycosis Mycoses Oncology Zygomycosis 758 758 1 09/25/23 20230929 NES 230929 2023 SEP 29 (NewsRx) -- By a News Reporter-Staff News Editor at Drug Week -- Fresh data on acute monocytic leukemia are presented in a new report. [Extracted from the article]
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- 2023
43. T-cell/myeloid mixed-phenotype acute leukemia with monocytic differentiation and isolated 17p deletion
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Germison Silva Lopes, João Paulo de Vasconcelos Leitão, Jacques Kaufman, Fernando Barroso Duarte, and Daniel Mazza Matos
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Acute monocytic leukemia ,Flow cytometry ,Chromosome deletion ,Antigens ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Mixed phenotype acute leukemia is a rare subtype of leukemia that probably arises from a hematopoietic pluripotent stem cell. The co-expression of two of myeloid, B- or T-lymphoid antigens is the hallmark of this disease. Herein, the case of a 28-year-old female patient is reported who presented with hemoglobin of 5.8 g/dL, white blood cell count of 138 × 109/L and platelet count of 12 × 109/L. The differential count of peripheral blood revealed 96% of blasts. Moreover, the patient presented with lymphadenopathy, splenomegaly and bone marrow infiltration by monocytoid blasts characterized as 7% positivity by Sudan Black cytochemical staining. Immunophenotyping revealed the involvement of blasts of both T- and monocytic lineages. The cytogenetic analysis showed an isolated 17p deletion. Thus, the diagnosis of T-cell/myeloid mixed phenotype acute leukemia was made with two particular rare features, that is, the monocytic differentiation and the 17p deletion as unique cytogenetic abnormalities. The possibility of concomitant expressions of T-cell and monocytic differentiation antigens in the same blast population is hard to explain using the classical model of hematopoiesis. However, recent studies have suggested that myeloid potential persists even when the lineage branches segregate toward B- and T-cells. The role of an isolated 17p deletion in the pathogenesis of this condition is unclear. At present, the patient is in complete remission after an allogeneic stem cell transplantation procedure.
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- 2014
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44. A case of acute monocytic leukemia (AMoL or AML‐M5) in an adult FeLV/FIV‐positive cat
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Joanne B. Messick and Priscila B S Serpa
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030213 general clinical medicine ,education.field_of_study ,Acute leukemia ,Pathology ,medicine.medical_specialty ,Myeloid ,General Veterinary ,040301 veterinary sciences ,Anemia ,Population ,04 agricultural and veterinary sciences ,medicine.disease ,0403 veterinary science ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,hemic and lymphatic diseases ,medicine ,Bone marrow ,Acute monocytic leukemia ,Leukocytosis ,medicine.symptom ,education ,Histiocyte - Abstract
A 7-year-old castrated male domestic shorthair cat was presented for evaluation of decreased appetite and respiratory signs. A CBC run on presentation revealed severe nonregenerative anemia, thrombocytopenia, and leukocytosis characterized by a prominent population of blasts, having morphologic features suggestive of a monocytic lineage. The cat tested positive for FIV, FeLV, Mycoplasma haemominutum, and only mild abnormalities were identified on the chemistry panel. Bone marrow biopsies were obtained to investigate the bicytopenia and the possibility of a hematopoietic neoplasm. Although the bone marrow aspirate was nondiagnostic, the core biopsy was markedly hypercellular with a population of blasts, largely replacing the normal hematopoietic tissue. Immunohistochemical staining revealed that the blasts were CD3-negative, Pax5-negative, dimly CD18-positive, and moderately positive for Iba1. These findings, in addition to the prominent monocytic differentiation seen in peripheral blood, supported a diagnosis of acute monocytic leukemia. Palliative antiviral and antibiotic treatment and blood transfusion were performed. The patient was discharged on his fourth day of hospitalization. However, 15 days following discharge, the cat was euthanized due to the worsening of his systemic signs. This report discusses the classifications of myeloid leukemias, implications of infectious diseases in the pathogenesis of neoplasia in cats, and the use of Iba1, a "pan-monocytic/histiocytic" marker, in the diagnosis of acute leukemia.
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- 2021
45. Identification of HLA-A*0201-restricted CTL Epitopes for MLAA-34-specific Immunotherapy for Acute Monocytic Leukemia
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Yun Yang, Ju Bai, Jianli Wang, Aili He, Wanggang Zhang, and Fang-Xia Wang
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CD4-Positive T-Lymphocytes ,0301 basic medicine ,Cancer Research ,THP-1 Cells ,Lymphocyte ,medicine.medical_treatment ,Immunology ,Epitopes, T-Lymphocyte ,Antineoplastic Agents ,Mice, SCID ,CD8-Positive T-Lymphocytes ,Epitope ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Antigens, Neoplasm ,Cell Line, Tumor ,HLA-A2 Antigen ,medicine ,Animals ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,Acute monocytic leukemia ,Pharmacology ,Chemistry ,Dendritic Cells ,U937 Cells ,Immunotherapy ,medicine.disease ,CTL ,030104 developmental biology ,medicine.anatomical_structure ,A549 Cells ,030220 oncology & carcinogenesis ,Leukemia, Monocytic, Acute ,MCF-7 Cells ,Peptide vaccine ,Apoptosis Regulatory Proteins ,Peptides ,CD8 ,T-Lymphocytes, Cytotoxic - Abstract
Our previous research has shown that monocytic leukemia-associated antigen-34 (MLAA-34) was a novel antiapoptotic molecule with unique expression in acute monocytic leukemia (M5), making it an ideal target for T-cell-based immunotherapy. Here, we sought to identify HLA-A*0201-restricted cytotoxic T-lymphocyte (CTL) epitope of MLAA-34 by reverse immunology. In all, 10 HLA-A*0201 restricted epitopes of MLAA-34 were predicted by bioinformatics. MLAA-34324-332, MLAA-34293-301, and MLAA-34236-244 showed the strongest HLA-A*0201-binding affinity. The percentages of HLA-A*0201-MLAA-34236-244 tetramer+ CD8+ T cells in MLAA-34236-244-induced CTLs were raised apparently. Enzyme-linked immunospot showed that MLAA-34236-244 and MLAA-34324-332-specific CTLs produced a higher amount of interferon-γ. MLAA-34236-244-induced CTLs presented a stronger cytotoxic effect on THP-1 cells (HLA-A*0201+MLAA-34+) at various effector to target ratios. MLAA-34236-244 peptide vaccine could inhibit the tumor growth and improve mean survival time of leukemia-bearing human peripheral blood lymphocyte reconstituting severe combined immunodeficient mice. Mice immunized with MLAA-34236-244 vaccine had increased percentages of MLAA-34236-244 tetramer+ CD8+ T cells in the spleen after each round of immunization. High-purity CD8+ and CD4+ T cells were sorted by Dynabeads as effector cells. The killing activity of CD8+ T cells was higher than that of CD4+ T cells. CTLs derived from the MLAA-34 peptide vaccine group were significantly higher than other therapeutic groups and showed specific cytotoxicity to THP-1 cells. Increased interferon-γ and interleukin (IL)-2 and decreased IL-10 and IL-4 were seen in the MLAA-34236-244 peptide vaccine group. MLAA-34236-244 peptide (ILDRHNFAI) is an effective HLA-A*0201-restricted CTL epitope and that it may serve as a promising strategy in designing antigen-specific immunotherapy against MLAA-34-positive acute monocytic leukemia.
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- 2021
46. Leukemia
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Isaacs, Hart, Jr.
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- 2002
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47. A case of rhinocerebral mucormycosis with brain abscess drained by endoscopic endonasal skull base surgery
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Tsuyoshi Ohta, Satoshi Oka, Seiichiro Makihara, Kenichi Kozakura, Kensuke Uraguchi, Takaya Higaki, Toshi Imai, Shin Kariya, Akira Doi, and Kazunori Nishizaki
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0301 basic medicine ,medicine.medical_specialty ,Endoscopic endonasal surgery ,030106 microbiology ,030231 tropical medicine ,Case Report ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,Remission Induction Therapy ,medicine ,Acute monocytic leukemia ,Abscess ,Brain abscess ,lcsh:QH301-705.5 ,lcsh:R5-920 ,medicine.diagnostic_test ,business.industry ,Mucormycosis ,Magnetic resonance imaging ,medicine.disease ,bacterial infections and mycoses ,Surgery ,Infectious Diseases ,lcsh:Biology (General) ,Endoscopic endonasal skull base surgery ,Rhinocerebral mucormycosis ,business ,lcsh:Medicine (General) ,Acute rhinosinusitis - Abstract
A 70-year-old Japanese man undergoing remission induction therapy for acute monocytic leukemia (AML-M5b) developed fever and headache, and was started on antibiotics and liposomal amphotericin B (L-AMB). There was no improvement, and computed tomography and contrast-enhanced magnetic resonance imaging revealed acute rhinosinusitis and brain abscess. Successful endoscopic endonasal surgery was performed at this point, providing drainage for the rhinosinusitis and abscess. Histopathological findings showed the mucormycosis.
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- 2020
48. IL‐1 signaling pathway molecules as key markers in childhood asthma
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Wenping Wei, Xingjie Ma, Yu Ma, Ling Fang, Chuangli Hao, Jiaqi Huang, and Wei Fang
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Ubiquitin-Protein Ligases ,Immunology ,Peripheral blood mononuclear cell ,Pathogenesis ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,Acute monocytic leukemia ,Child ,Asthma ,House dust mite ,biology ,business.industry ,Nuclear Proteins ,biology.organism_classification ,medicine.disease ,IRAK2 ,Ovalbumin ,030228 respiratory system ,Pediatrics, Perinatology and Child Health ,Leukocytes, Mononuclear ,biology.protein ,Signal transduction ,business ,Biomarkers ,Interleukin-1 ,Signal Transduction - Abstract
Objective The prevalence of childhood asthma has been increasing in recent years. This study aims to investigate the involvement of the key molecules of IL-1 (interleukin-1) signaling pathways in pediatric patients with asthma. Methods Differentially expressed genes (DEGs) associated with IL-1 signaling pathways were identified with RNA-seq from peripheral blood samples collected from asthmatic or healthy children and were further verified in clinical peripheral blood samples. Cellular models and asthmatic mice were subsequently developed to validate the identified asthmatic markers. Results Among the DEGs identified by RNA-seq, eight signal transducers associated with the IL-1 signaling network, namely IL-1RN, IL-1β, IL-1RAP, IRAK3, IL-1R1, MYD88, IRAK2 and PELI1, were found to be substantially upregulated in children with asthma. Interestingly, a significant serially increased expression of four genes (IL-1RN, IL-1RAP, IRAK3 and PELI1) were observed in healthy subjects, patients with chronic persistent asthma and patients with acute exacerbation asthma. In particular, these four genes were continuously overexpressed in recurrent patients. A significant induction of the above four genes was then observed in house dust mite (HDM)-stimulated peripheral blood mononuclear cells (PBMCs) and ovalbumin (OVA)-induced asthmatic mice. In addition, a time-dependent induction of IL-1RAP and PELI1 was also detected in HDM-treated THP-1 cells, an acute monocytic leukemia cell line. Conclusions These results demonstrate that IL-1RN, IL-1RAP, IRAK3 and PELI1, which are signal transducers of the IL-1 signaling pathway, could serve as biomarkers for the pathogenesis of childhood asthma and for potential therapeutic targets of asthma.
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- 2020
49. Plasmacytoid Dendritic Cell Infiltration in Acute Myeloid Leukemia
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Jiali Li, Ping Wang, Wei Zhang, Jun Rao, Chao Yang, Pei-Yan Kong, Lidan Zhu, Jingkang Xiong, Xi Zhang, Jiang F. Zhong, Yao Liu, Qiong Li, Deng Xiaojuan, and Xian-Gui Peng
- Subjects
0301 basic medicine ,business.industry ,medicine.medical_treatment ,Myeloid leukemia ,Chronic myelomonocytic leukemia ,hemic and immune systems ,macromolecular substances ,Plasmacytoid dendritic cell ,Hematopoietic stem cell transplantation ,medicine.disease ,03 medical and health sciences ,Leukemia ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,Acute myelomonocytic leukemia ,medicine ,Cancer research ,Bone marrow ,Acute monocytic leukemia ,business - Abstract
Introduction Increasing evidence has demonstrated that plasmacytoid dendritic cells (PDCs) in the tumor microenvironment (TME) play an important role in tumorigenesis and progression. PDC infiltration has been found in certain malignancies such as classic Hodgkin's lymphoma and chronic myelomonocytic leukemia. Our previous work reported that PDC infiltration could occur in acute myeloid leukemia (AML), but the clinical significance of PDC in AML has not been thoroughly investigated. Patients and methods Here, we evaluated the clinical significance of PDC to AML transition in a leukemia microenvironment. The frequency of PDCs in 80 acute myelomonocytic leukemia (AML-M4) and 83 acute monocytic leukemia (AML-M5) patients was determined by flow cytometry. Results We found 62 cases with PDC infiltration. These patients showed higher numbers of bone marrow blasts, higher mean Hb concentration, and required more cycles of chemotherapy before achieving complete remission (CR), but had lower white blood cell and platelet counts compared to patients without PDC infiltration. Drug sensitivity analysis showed that patients with PDC infiltration had lower sensitivity to standard chemotherapy regimens. Kaplan-Meier survival curves demonstrated that patients with PDC infiltration had a shorter overall survival (OS) time and progression-free survival time. Discussion These results suggested that PDC infiltration can be used for risk stratification of AML-M4/M5, and PDCs may transdifferentiate into leukemia in an AML microenvironment.
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- 2020
50. NM23-H1 Protein Expression as a New Prognostic Factor in Acute Lymphoblastic Leukemia
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Höchsmann, B., Müller, E., Heil, G., Frickhofen, N., Bergmann, L., Büchner, T., editor, Hiddemann, W., editor, Wörmann, B., editor, Schellong, G., editor, Ritter, J., editor, and Creutzig, U., editor
- Published
- 2001
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