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The presented case report describes an incredibly rare instance of an intramedullary bronchial cyst located in the thoracic spinal canal on the dorsal side of the spinal cord, which was observed in a patient with chronic myelogenous leukemia. A 29-year-old man presented with back pain for half a month, along with numbness and pain below the chest and ribs for 1 week. Hypersensitivity was present in the inferior plane of the long xiphoid process in the nervous system. Magnetic resonance imaging (MRI) showed intramedullary cystic lesions in the vertebral body plane of the third to the fourth thoracic vertebra. There was no recurrence during the 6-month postoperative follow-up period. The histopathological findings were consistent with bronchogenic cysts. Cystic lesions were eliminated through the posterior median approach. After the cyst ruptured during surgery, gel liquid was seen, and the majority of the cyst walls were removed. One week after the surgery, the hypersensitivity fully subsided. Six months following surgery, an updated MRI revealed no recurrence. Intramedullary bronchogenic cysts on the dorsal side of the thoracic spine are extremely uncommon. Diagnosis requires histopathological evidence, and it is challenging to diagnose before surgery. Prompt surgical resection is recommended in case of positive diagnosis.

Purpose: In this study, we report a patient who presented with both chronic myelocytic leukemia (CML) and Susac syndrome (SS). Observations: A 45-year-old male diagnosed with CML in the blast phase sought consultation due to a deterioration in vision in his right eye. He also had hearing loss and severe migraneous headaches. Best corrected visual acuity was light perception and 20/20 in the right and left eyes, respectively. The slit lamp examination and intraocular pressure were within normal ranges for both eyes. Upon dilated fundoscopy, organized vitreous hemorrhage was observed in the right eye, while the left eye exhibited extensive sclerotic vessels with retinal neovascularization in the periphery. Ultrasound of the right eye showed tractional retinal detachment. Optical coherence tomography of the left retina showed thinning of the retina in temporal macula. Fluorescein angiography revealed a substantial nonperfused region in the peripheral left retina, accompanied by arterioarterial and arteriovenous collaterals, along with microaneurysms. MRI showed scattered foci of hyperintensity within the supratentorial white matter, mostly subcortical on T2-weighted and fluid-attenuated inversion-recovery. The patient received a diagnosis of SS and was subsequently referred to the neurology service for further assessment and potential treatment. Conclusion and importance: SS may manifest as a presentation of CML. It is advisable to conduct investigations for SS in CML patients experiencing neurological, ophthalmological, or otological symptoms.

Objective To construct the chronic myeloid leukemia (CML) K562 cell line with overexpression of human tongue cancer drug resistance related gene (TCRP1) by lentivirus vector and to test its biological function. Methods The recombinant plasmid of TCRP1 and the packaging plasmid were co-transfected into 293T cells, and the K562 cells were infected after the titer of the virus was determined. Puromycin was used to screen TCRP1 overexpression cell line K562/TCRP1, and the expression of TCRP1 was detected by fluorescence quantitative PCR and Western blot. The proliferation of K562/TCRP1 and its control cell line was detected by continuous cell counting method and CCK-8 method respectively. The drug sensitivity of the two cell lines to different concentrations of imatinib (IM) was analyzed. Results The TCRP1 lentivirus expression vector was successfully transfected into K562 cells. The results of fluorescence quantitative PCR and Western blot showed that the expression of TCRP1 in K562/TCRP1 cell line was significantly higher than that in the control group at the level of mRNA and protein. The results of continuous cell counting and CCK-8 methods showed that the proliferation of K562/TCRP1 cells were enhanced, and the IC50 value of IM-treated K562/TCRP1 cells was significantly higher than that of the control cells (P < 0.05) . Conclusion The K562 cell line with overexpression of TCRP1 was successfully constructed using lentivirus vector, and we found that the overexpression of TCRP1 might enhance the proliferation and IM resistance of K562 cells, which provided a basis for further exploring the possible role of TCRP1 in the pathogenesis of chronic myeloid leukemia. [ABSTRACT FROM AUTHOR]

Src is overexpressed in various cancers, including 27% of non-small cell lung cancer NSCLC, and is correlated with poor clinical outcomes. We hypothesize that Src kinase inhibitors, including Bosutinib, may exhibit clinical synergy in combination with the antifolate drug pemetrexed. In this Phase I, dose-escalation, safety, and maximum tolerated dose (MTD)-determining study, 14 patients with advanced metastatic solid tumors that had progressed on “standard of care” chemotherapy were enrolled in a 3 + 3 dose escalation study. Oral Bosutinib was administered once daily beginning on day 1, where the first cohort started at an oral dose of 200 mg daily with pemetrexed 500 mg/m2 IV on a three-week schedule. The study’s primary objective was to determine the dose-limiting toxicity (DLT), the MTD of Bosutinib in combination with pemetrexed, and the type and frequency of adverse events associated with this treatment. Twelve patients were evaluable for response, including ten patients with adenocarcinoma of the lung, one patient with metastatic adenocarcinoma of the appendix, and one patient with urothelial carcinoma. The median number of Bosutinib and pemetrexed cycles received was 4 (range, 1–4). The MTD of oral Bosutinib in this combination was 300 mg daily. Two patients (17%) had a partial response (PR), and seven patients (58%) showed stable disease (SD) as the best response after the fourth cycle (end of treatment). One patient had disease progression after the second cycle, while three patients had disease progression after the fourth cycle. The two responders and the two patients with the longest stable disease duration or stabilization of disease following progression on multiple systemic therapies demonstrated Src overexpression on immunohistochemical staining of their tumor. The median progression-free survival (PFS) was 6.89 months (95% CI (3.48, 30.85)), and the median overall survival (OS) was 11.7 months (95% CI (3.87, 30.85)). Despite the limitations of this Phase I study, there appears to be potential efficacy of this combination in previously treated patients.

Src is overexpressed in various cancers, including 27% of non-small cell lung cancer NSCLC, and is correlated with poor clinical outcomes. We hypothesize that Src kinase inhibitors, including Bosutinib, may exhibit clinical synergy in combination with the antifolate drug pemetrexed. In this Phase I, dose-escalation, safety, and maximum tolerated dose (MTD)-determining study, 14 patients with advanced metastatic solid tumors that had progressed on "standard of care" chemotherapy were enrolled in a 3 + 3 dose escalation study. Oral Bosutinib was administered once daily beginning on day 1, where the first cohort started at an oral dose of 200 mg daily with pemetrexed 500 mg/m2 IV on a three-week schedule. The study's primary objective was to determine the dose-limiting toxicity (DLT), the MTD of Bosutinib in combination with pemetrexed, and the type and frequency of adverse events associated with this treatment. Twelve patients were evaluable for response, including ten patients with adenocarcinoma of the lung, one patient with metastatic adenocarcinoma of the appendix, and one patient with urothelial carcinoma. The median number of Bosutinib and pemetrexed cycles received was 4 (range, 1–4). The MTD of oral Bosutinib in this combination was 300 mg daily. Two patients (17%) had a partial response (PR), and seven patients (58%) showed stable disease (SD) as the best response after the fourth cycle (end of treatment). One patient had disease progression after the second cycle, while three patients had disease progression after the fourth cycle. The two responders and the two patients with the longest stable disease duration or stabilization of disease following progression on multiple systemic therapies demonstrated Src overexpression on immunohistochemical staining of their tumor. The median progression-free survival (PFS) was 6.89 months (95% CI (3.48, 30.85)), and the median overall survival (OS) was 11.7 months (95% CI (3.87, 30.85)). Despite the limitations of this Phase I study, there appears to be potential efficacy of this combination in previously treated patients. [ABSTRACT FROM AUTHOR]

Background: Effective treatments for hematologic malignancies include therapies that target tyrosine kinase (TK) signaling pathways. Tumor lysis syndrome (TLS) is an oncologic emergency that can occur due to rapid turnover following the initiation of treatments for hematologic malignancy. The incidence of TLS is under‐reported and it is unclear as to whether TK inhibitors (TKIs) are associated with TLS. Objective: To conduct a systematic review to determine the incidence of TLS with TKIs. Methods: A search was performed using EMBASE, MEDLINE, and Web of Science electronic databases, as well as a manual search of the American Society of Hematology and American Society of Clinical Oncology abstract databases. Keywords included: "tumor lysis syndrome," "tyrosine kinase inhibitors," "lymphoma," and "leukemia." Results: We identified a total of 57 publications that commented on the incidence of TLS with TKIs for hematologic malignancy. Thirty‐nine of those publications reported TLS as an adverse event. TLS was described as an adverse event among essentially all the subclasses of TKIs that are used to manage hematologic malignancies. Conclusion: The overall number of articles commenting on TLS as an adverse event is sparse and there needs to be more transparency regarding the incidence of TLS when employing newer targeted therapies. Physicians should consider the risk of TLS on an individual basis and the added risk of TLS when using TKIs to treat hematologic malignancy. [ABSTRACT FROM AUTHOR]

The BCR-ABL mutation is the main cause of tyrosine kinase inhibitors(TKI) resistance. The second-generation TKI can overcome most of the mutations. However, both dasatinib and nilotinib have a unique set of mutants with reduced sensitivity. All TKIs are associated with adverse events, which lead to treatment discontinuation and affect the quality of life of patients. Flumatinib showed higher activity against BCR-ABL mutants in vitro. Drug-related adverse events of flumatinib were mainly grade 1 or grade 2 events. There is no study that reported the efficacy of flumatinib against F359V/C mutation.We report two cases of chronic myelocytic leukemia(CML) patients with F359V/C mutation resistance to Imatinib therapy. One patient with F359V mutation was shifted to Dasatinib. Repeated massive pleural effusion and anemia occurred after Dasatinib treatment, forcing drug dosage reduction or withdrawal, affecting drug efficacy and quality of life of patient. Two patients were shifted to Flumatinib. MR4 was achieved and F359V/C mutation was not detected after treatment with Flumatinib. There was no significant side effect. The patients had a high quality of life. Flumatinib is effective against F359V/C mutation, has less drugrelated adverse reactions. Flumatinib may be a better choice for patients with F359V/C mutation. [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by a fusion gene, encoding for the chimeric protein BCR-ABL, with constitutive tyrosine kinase activity. The use of tyrosine kinase inhibitors (TKIs) has drastically improved survival, but there are significant concerns about cardiovascular toxicity. Cardiovascular risk can be lowered with appropriate baseline evaluation, accurate choice of TKI therapy, improvement of modifiable cardiovascular risk factors through lifestyle modifications, and prescription of drugs for primary or secondary prevention. Which examinations are necessary, and when do they have to be scheduled? How often should a TKI-treated patient undergo which cardiology test or exam? Is there an accurate way to estimate the risk that each TKI may determine a cardiovascular adverse event in a CML patient? In a few words, how can we optimize the cardiovascular risk management in CML patients before and during TKI treatment? The aim of this review is to describe cardiac and vascular toxicity of TKIs used for CML treatment according to the most recent literature and to identify unmet clinical needs in cardiovascular risk management and complications in these patients. Regarding the TKI-induced cardiovascular toxicity, the full mechanism is still unclear, but it is accepted that different factors may play different roles: endothelial damage and atherosclerosis, metabolic impairment, hypertensive effect, glomerular impairment, and mast-cell disruption. Preventive strategies are aimed at minimizing cardiovascular risk when CML is diagnosed. Cardio-oncology units in specialized hematology centers may afford a personalized and multidisciplinary approach to the patient, optimizing the balance between treatment of the neoplasm and management of cardiovascular risk.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by a fusion gene, encoding for the chimeric protein BCR-ABL, with constitutive tyrosine kinase activity. The use of tyrosine kinase inhibitors (TKIs) has drastically improved survival, but there are significant concerns about cardiovascular toxicity. Cardiovascular risk can be lowered with appropriate baseline evaluation, accurate choice of TKI therapy, improvement of modifiable cardiovascular risk factors through lifestyle modifications, and prescription of drugs for primary or secondary prevention. Which examinations are necessary, and when do they have to be scheduled? How often should a TKI-treated patient undergo which cardiology test or exam? Is there an accurate way to estimate the risk that each TKI may determine a cardiovascular adverse event in a CML patient? In a few words, how can we optimize the cardiovascular risk management in CML patients before and during TKI treatment? The aim of this review is to describe cardiac and vascular toxicity of TKIs used for CML treatment according to the most recent literature and to identify unmet clinical needs in cardiovascular risk management and complications in these patients. Regarding the TKI-induced cardiovascular toxicity, the full mechanism is still unclear, but it is accepted that different factors may play different roles: endothelial damage and atherosclerosis, metabolic impairment, hypertensive effect, glomerular impairment, and mast-cell disruption. Preventive strategies are aimed at minimizing cardiovascular risk when CML is diagnosed. Cardio-oncology units in specialized hematology centers may afford a personalized and multidisciplinary approach to the patient, optimizing the balance between treatment of the neoplasm and management of cardiovascular risk. [ABSTRACT FROM AUTHOR]

In this case report, we describe a case of imatinib leading to a falsepositive amphetamine result on urine drug testing. A 21-year-old female with chronic myelocytic leukemia and in recovery from opioid use disorder reinitiated imatinib maintenance therapy in her third trimester, after previous discontinuation at the beginning of pregnancy. Subsequently, she had multiple presumptive immunoassay- based urine drug tests that resulted positive for amphetamines. The infant's meconium testing was negative for amphetamines, as was maternal definitive testing using urine gas chromatography-mass spectrometry. She had no history of stimulant use and denied any substance use during her pregnancy. Imatinib and/or its metabolites may be responsible for cross-reactivity with urine drug immunoassays leading to a false-positive result for amphetamine. [ABSTRACT FROM AUTHOR]

[Display omitted] • A split-type electrochemical DNA sensor using enzyme-linked DNA magnetic beads. • Duplex ligase chain reaction and OR logic gate are intergrated into this biosensor. • The electrochemical biosensor exhibits excellent performance in real sample assay. • This biosensor is promising for clinical application of chronic myelocytic leukemia. Detection of BCR/ABLp210 transcript levels, allowing for the early diagnosis of chronic myelocytic leukemia (CML) and its minimal residual disease (MRD) monitoring, plays a decisive role in the cure of CML. Herein, to realize the sensitive detection of BCR/ABLp210 transcript by electrchemical DNA (E-DNA) sensors in clinical samples, a split-type strategy using enzyme-linked DNA magnetic beads (MBs) was intelligently provided. Specifically, the utilization of magnetic separation makes the target recognition event separate from electrochemical measurements, avoiding the interference of complex matrices on the sensing interface. Besides, the MBs adopted as dispersible electrodes could improve mass transfer of target compared to that of a planar electrode. Consequently, the proposed E-DNA sensor combined with the ligation chain reaction (LCR) could achieve an exceptional performance with a low detection limit of 1 aM, a broad linear concentration range, and a remarkable specificity with a single-base resolution. Also, K562 cells in up to a 1000-fold excess of NB4 cells could be successfully detected by this E-DNA sensor. Finally, the integration of duplex LCR and OR logic gate into the E-DNA sensor has enabled the detection of e13a2/e14a2/both isoforms of BCR/ABLp210 transcript in a single assay in both newly diagnosed CML patients and those undergoing or having undergone treatment by tyrosine kinase inhibitors. Therefore, this method offers an alternative for the early diagnosis of CML and its MRD monitoring, and holds a huge potential of clinical translation due to its advantage of low cost, ease of miniaturization and generalizability. [ABSTRACT FROM AUTHOR]

Hereditary spherocytosis (HS) and Chronic myelocytic leukemia (CML) are both life threatening hemotologic diseases. They are rarely seen to occur simultaneously in one individual patient. Here we demonstrate a case of HS associated with CML in this study. The patient is a young female, diagnosed with HS in 2005, and was given partial embolization of the splenic artery. She got significant remission after the procedure. In 2008, she was found abnormal in blood routine test, after bone marrow routine, chromosome and fusion gene tests, she was diagnosed with CML (chronic phase). She did not receive regular treatment until 3 months prior, and is currently being treated with Dasatimib. She achieved hematological remission, but had no significant improvement in chromosome and fusion gene figures. Due to her severe condition of hemolysis, a splenectomy or an allogeneic hematopoietic stem cell transplantation is considered.

The aim of the present study was to investigate the regulation of Wilms Tumor 1 (WT1) by serine protease high-temperature requirement protein A2 (HtrA2), a member of the Htr family, in K562 cells. In addition, the study aimed to observe the effect of this regulation on cell biological functions and its associated mechanisms. Expression of WT1 and HtrA2 mRNA, and proteins following imatinib and the HtrA2 inhibitor 5-[5-(2-nitrophenyl) furfuryl iodine]-1, 3-diphenyl-2-thiobarbituric acid (UCF-101) treatment was detected with reverse transcription-quantitative polymerase chain reaction and western blot analysis. Subsequent to treatment with drugs and UCF-101, the proliferative function of K562 cells was detected using MTT assays, and the rate of apoptosis was detected using Annexin V with propidium iodide flow cytometry in K562 cells. The protein levels in the signaling pathway were analyzed using western blotting following treatment with imatinib and UCF-101. In K562 cells, imatinib treatment activated HtrA2 gene at a transcription level, while the WT1 gene was simultaneously downregulated. Following HtrA2 inhibitor (UCF-101) treatment, the downregulation of WT1 increased gradually. At the protein level, imatinib induced the increase in HtrA2 protein level and concomitantly downregulated WT1 protein level. Subsequent to HtrA2 inhibition by UCF-101, the WT1 protein level decreased temporarily, but eventually increased. Imatinib induced apoptosis in K562 cells, but this effect was attenuated by the HtrA2 inhibitor UCF-101, resulting in the upregulation of the WT1 protein level. However; UCF-101 did not markedly change the proliferation inhibition caused by imatinib. Imatinib activated the p38 mitogen activated protein kinase (p38 MAPK) signaling pathway in K562 cells, and UCF-101 affected the activation of imatinib in the p38 MAPK signaling pathway. Imatinib inhibited the extracellular signal-related kinase (ERK1/2) pathway markedly and persistently, but UCF-101 exhibited no notable effect on the inhibition of the ERK1/2 pathway. HtrA2 and its regulatory effect on WT1 may affect the sensitivity of BCR/ABL(+) cell lines to target therapy drugs through different mechanisms. Regulation of WT1 by HtrA2 occurs in K562 cells, and the regulation may affect the apoptosis of K562 cells under the stress caused by chemotherapeutic treatment. The p38 MAPK signaling pathway, which serves an important role in cell apoptosis, is a downstream pathway of this regulation. [ABSTRACT FROM AUTHOR]

Imatinib mesylate is a tyrosine kinase inhibitor used in the treatment of several malignancies. Its use, however, is associated with a number of toxic effects including adverse cutaneous reactions. Herein, we present a case of facial cystic acne in a patient receiving imatinib therapy for chronic myelocytic leukemia. This side effect resolved with cessation of therapy. To the best of our knowledge, this clinical entity has never been previously reported in the medical literature. [ABSTRACT FROM AUTHOR]

"n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 st1":*{behavior:url(#ieooui) } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Lactobacillus species are genetically diverse groups of Lactic Acid Bacteria (LAB) that have been introduced as probiotics, because of some characteristics such as their anti-tumor properties, helping the intestinal flora balance, production of antibiotics, stimulation of host immune response, etc. The aim of this study was to investigate the effects of cytoplasmic extraction and cell wall of Lactobacillus species isolated from the intestine of common carp on human chronic myelocytic leukemia or K562 cancer cell lines."n"nMethods: The intestinal contents of 115 common carp captured from the natural resources of West Azerbaijan province in Iran were examined for LAB. After isolation, the identification of Lactobacilli was done according to traditional and molecular bacteriological tests. Subsequently, a suspension of each bacterium was prepared and the protein content of the cytoplasm was extracted. Cell wall disintegration was done by cell lysis buffer and sonication. The effects of cytoplasmic extraction and cell wall on K562 cell line proliferation were investigated by MTT assays."n"nResults: The cytoplasmic extraction of the isolated Lactobacilli had significant (p

The oncogenic bcr/abl1 fusion gene is a chronic myelogenous leukemia (CML)-specific antigen which is absent in normal tissues. This makes bcr/abl1 a perfect target for developing CML vaccines that elicit specific immune responses against minimal residual disease while sparing normal tissue. The aim of this study was to use different methods to induce dendritic cells (DCs) derived from patients with CML (CML-DCs) and analyze them for CML-specific tumor cytotoxicity for immune therapy. Bone marrow-derived mononuclear cells from ten CML patients were studied to induce CML-DC differentiation in the presence of recombinant human interleukin-4, rh-granulocyte-macrophage-colony stimulating factor, and tumor necrosis factor-alpha with either a total RNA-lipofectamine complex, total RNA or CML tumor lysate (freeze-thawed). CML-DC maturation, confirmed by expression of CD1α, CD40, CD80, CD83, CD86 and by real-time polymerase chain reaction, validated the CML-origin of these DC cells. CML-DCs stimulated cytotoxic T-cell (CTL) apoptosis, high levels of IL-12 secretion, and had significant inhibitory effect on K562 tumorigenicity in nude mice. CML-DCs pulsed with total RNA by lipofectamine transfection produced the strongest effect in tumor-specific CTL functions. These results indicate that CML-DCs transfected with total RNA by lipofectamine induce the strongest CTL cytotoxicity and have the greatest potential for CML immune therapy. This study holds promise for a DC-based strategy for inducing anti-leukemia responses and establishes a foundation for developing RNA vaccination against CML. [ABSTRACT FROM AUTHOR]

The current study reports a case of a patient with a chronic myelocytic leukemic fundus lesion, initially diagnosed in the Department of Ophthalmology, Rizhao People's Hospital (Rizhao, China). A male, 23-years-of-age, presented with a dark shadow in the front of the right eye, accompanied with blurred vision for 3 days (visual acuity of right eye, 0.4; visual acuity of left eye, 0.6). In addition, the patient had experienced gingival bleeding for 2 years, and recurrent upper respiratory infections for 1 year. A fundus examination revealed mild binocular papillary edema, dilated and tortuous veins, and the retina exhibited large quantities of scattered and dark red bleeding spots. The bleeding spots had white spots in the center, which exhibited typical Roth spots, whilst routine blood examination, abdominal ultrasound, marrow biopsy and other laboratory tests confirmed the diagnosis of chronic myelogenous leukemia. Patients with leukemia typically present with initial symptoms that include fever, fatigue, anemia and hepatosplenomegaly, and a diagnosis as a result of eye-related symptoms is rare, rendering the present case unique. [ABSTRACT FROM AUTHOR]

Imatinib is an important example of tyrosine kinase inhibitors (TKIs) used in clinical practice. Imatinib blocks the ATP binding site of the Bcr-Abl fusion protein and selectively inhibits Bcr-Abl tyrosine kinase (TK) activity. Treatment of chronic myelocytic leukemia (CML) with imatinib is encouraging and it has an acceptable toxicity profile, and as such has changed the management of CML during the last decade. As with all drugs used in clinical practice, side effects of imatinib have been reported in studies with extended follow-up periods. In addition, some neoplastic disorders have been reported to occur during imatinib therapy. Herein we present a CML case that developed non-Hodgkin’s lymphoma (NHL) while receiving imatinib treatment.

In 2012, a 25-years-old pregnant woman presented with thromocytosis for 4 months, blood counts showed platelets 701 × 10/L. Bone marrow examination disclosed a feature of hypercellular marrow in erythrocytic,granulocytic and megakaryocytic series. Cytogenetic analysis showed t(9;22)(q34;q11) in 100 % of metaphase. The percentage of BCR-ABL-positive FISH signals was 37 % in the peripheral blood. Molecular analysis showed the presence of the JAK2V617F mutation and BCR-ABL mRNA b3a2 transcript. A diagnosis of concomitant presence of essential thrombocythemia and chronic myelocytic leukemia was made. Based on this case and literatures reported before, it might be necessary to detect JAK2-V617F mutation and BCR-ABL fusion gene concomitantly in myeloproliferative neoplasms patients. [ABSTRACT FROM AUTHOR]

To detect the expression of cancerous inhibitor of phosphatase 2A (CIP2A) in chronic myelocytic leukemia (CML) and investigate the mechanism underlying CIP2A knockdown-mediated cell proliferation and apoptosis as well as the interaction of CIP2A with breakpoint cluster region-Abelson leukemia virus (BCR-ABL). CIP2A mRNA and protein expression in chronic myelocytic leukemia-chronic (CML-CP) patients and healthy controls were determined by RT-PCR and Western blot. In vivo, c-Myc expression, PP2A activity, cell proliferation, and apoptosis of CML cells were detected with CIP2A depletion. In addition, the relationship among CIP2A, BCR-ABL, and tyrosine phosphatase SHP-1 was explored by depleting/overexpressing CIP2A or inhibiting BCR-ABL. The level of CIP2A mRNA was higher in CML-CP patients than healthy controls (56/74, 75.7 % vs. 1/35, 2.9 %, P < 0.001), and CIP2A protein was overexpressed in corresponding specimens. CIP2A knockdown by siRNA reduced the level of c-Myc protein and clonogenic formation, inhibited the activity of PP2A, K562 cell proliferation, and promoted cell apoptosis. Suppressing BCR-ABL by imatinib mesylate (IM) significantly decreased CIP2A expression. CIP2A knockdown decreased BCR-ABL but increased SHP-1 expression, and CIP2A overexpression had the reverse effect. CIP2A is overexpressed in CML-CP patients, and its expression may promote CML pathogenesis. CIP2A and BCR-ABL can regulate each other in a positive feedback loop. CIP2A may be a useful therapeutic target in CML-CP, particularly in patients with IM resistance. However, further studies are needed to validate the interaction between CIP2A and BCR-ABL using other tyrosine kinase inhibitors than IM. [ABSTRACT FROM AUTHOR]

Imatinib is a tailored drug for the treatment of chronic myeloid leukemia (CML), and has substantial activity and a favorable safety profile when used as a single agent in patients with CML in myeloid blast crisis. The megakaryocytic blast crisis in CML occurs rarely and carries a poor prognosis. The aim of the present study was to investigate the effects of imatinib on cluster of differentiation (CD)34+ cells from patients with CML in the megakaryocytic crisis phase. Bone marrow mononuclear cells (BMNCs) were isolated from patients with CML in the megakaryocytic crisis phase. CD34+ cells were selected from BMNCs by positive immunomagnetic column separation. Imatinib significantly induced G1 arrest, reduced the phosphorylation of cyclin-dependent kinase 1 and retinoblastoma proteins and inhibited the proliferation of CD34+ cells from patients with CML in the megakaryocytic crisis phase. Annexin V/propidium iodide and caspase-3 activity showed that imatinib induced apoptosis. Western blot analysis and protein tyrosine kinase activity assays showed that imatinib inhibited BCR-ABL protein tyrosine kinase activity. The in vitro data thus markedly indicate a potential clinical application of imatinib for patients with CML in the megakaryocytic crisis phase. [ABSTRACT FROM AUTHOR]

Abstract: Activation-induced deaminase (AID), a cytidine deaminase, can accelerate the acquisition of BCR-ABL1 kinase domain mutations in human CML. In the present study, we investigated the expression of AID and Bcr-Abl in CML cells derived from 35 clinical patients. We found that both AID and Bcr-Abl were correlatively over-expressed in CML-LBC (lymphoid blast crisis) cells as compared with those in CML-CP (chronic phase) cells. AID expression was significantly decreased in CML-LBC cells after treated with arsenic trioxide, especially together with imatinib. We also observed satisfied therapy effects of As2O3 and imatinib on patients with CML blast crisis. These data suggest that decreasing AID expression in CML-LBC by As2O3 may be a promising approach to CML treatment. [Copyright &y& Elsevier]

Introduction. The survival of patients with chronic myelocytic leukemia (CML) has improved during the past decades. However, there have been discrepancies between results reported from clinical trials and population-based studies. We aimed to elucidate the extent of these discrepancies. Methods. We examined the 5-year survival rate of patients in clinical trials of CML treatment and compared these results with the survival of patients in the general population using the Surveillance, Epidemiology, and End Results (SEER) database, correcting for differences in the age structure of the patient populations. Results. Twenty-nine trials were identified for data extraction. The survival rate calculated from SEER data was lower than the survival rate in clinical trials in the corresponding period, with differences of 2.1%- 50.7%. Age-adapted survival was similar for four trials, but differences up to 35.8% were seen in most. Limitations of the study include the lack of information on chemotherapy in the SEER database and possible heterogeneity of cases. Discussion. The survival rate in clinical trials of CML treatment is higher than the survival rate of all patients with CML. We speculate that the difference may be a result of access to better medications, selection of healthier patients for trials, and the time necessary for adoption of new treatments. This finding underscores the need for population-based studies to give a more realistic idea of survival for patients with a given malignancy in the general population. [ABSTRACT FROM AUTHOR]

Abstract: Within the past 10–15 years, major advances in therapy have strongly improved prognosis of patients with chronic myelocytic leukaemia (CML). We estimated trends in 5- and 10-year relative survival of patients developing CML after a previous malignancy in the United States from 1990–1994 to 2000–2004. Period analysis was employed to disclose recent developments with minimum delay. Overall, 5- and 10-year relative survival increased from 17.6% to 37.7% (p <0.0001) and from 7.6% to 23.8% (p <0.0001), respectively. Improvements were particularly strong in younger age groups. Prognosis of CML patients with previous malignancy no longer lags behind prognosis of patients with primary CML. [Copyright &y& Elsevier]

Objective: The aim of the present case-control study was to determine whether or not the prevalence of gallbladder stones (GBS) was increased in patients with chronic myelocytic leukemia (CML) and to investigate clinical and laboratory characteristics of CML patients with GBS. Subjects and Methods: This study included 56 patients with CML and 55 sex- and age-matched healthy controls. All participants underwent abdominal ultrasonography and the main clinical and laboratory characteristics were recorded. Results: Gallbladder stones were detected in 13 (23.6%) patients with CML and in 3 (5.4%) control individuals (p < 0.05). The mean follow-up period of CML patients after diagnosis was 54.6 months, range 3–120 months. Hemoglobin levels were higher in the control group than in CML patients. However, total bilirubin, unconjugated bilirubin, lactate dehydrogenase levels, leukocyte and thrombocyte counts, frequency of splenomegaly and hepatomegaly were higher in the CML than in the control group (p < 0.05). Other clinical and laboratory values were not significantly different between the groups. CML patients with and without GBS were also compared for clinical and laboratory values. Age and follow-up period of CML patients after diagnosis were higher in the CML patients with GBS (p < 0.05). Conclusions: Higher prevalence of GBS in CML patients than in healthy controls was detected. We suggest that CML may increase the frequency of GBS, apart from other well-known risk factors. This risk is probably related to increased unconjugated bilirubin, which determines hemolysis, older age and long follow-up period of CML patients after diagnosis. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: There has been remarkable progress in our understanding of plasma cell dyscrasias and leukemias in recent years. New prognostic factors have come to light. Del(1)(p12) and t(4;14) confer poor prognoses on patients with myeloma. COX-2 positivity is associated with poorer progression-free and overall survival in myeloma patients and a role for COX-2 inhibitors in myeloma has been suggested. Thalidomide (400mg/day) and dexamethasone (20mg/m2 daily for 4 days) has emerged as first-line treatment for myelomas. Serious toxicities have been recognized, however. The thalidomide derivative, lenalidomide may be more active and less toxic than the parent compound and may replace it. Lenolidomide is also highly active against 5q-syndrome. Bortezomib is at least as active as thalidomide and less toxic, and the two drugs are not cross-resistant. Although marrow transplantation was the standard of care for newly diagnosed myeloma patients, recent prospective randomized studies cast doubt on its role. ZAP-70 and CD38 expression have major prognostic impact on outcome of chronic lymphocytic leukemia (CLL). The former may be a stronger predictor of the need for treatment than the presence of an unmutated IgV(H) gene. Although fludarabine is highly active in CLL, it may be associated with a higher number of second malignancies than are other treatments. Rituximab has major activity against CLL. However, at standard dose its effectiveness is limited by the fact that CD20 density is relatively low on CLL cells and circulating CD20 binds a significant fraction of administered drug. Either combining rituximab with other agents, or giving it in mega doses, which are safe and highly effective, can overcome these impediments. Imatinib has revolutionized the treatment of chronic phase chronic myelocytic leukemia (CML) and markedly decreased the number of allogeneic bone marrow transplants done for this neoplasm. However, the development of rapid resistance to the agent in blast crisis of CML or Philadelphia chromosome-positive acute lymphocytic leukemia gives the agent only a minor role in those diseases. More effective tyrosine kinase inhibitors currently under development may prove to be more useful in acute leukemias with the Philadelphia chromosome. Clofarabine is a successful new drug for acute myeloid leukemias of childhood and juvenile myelomonocytic leukemia. Drugs such as gemtuzumab ozogamicin, FLT3 inhibitors and farnesyl transferase inhibitors have been disappointing in acute leukemia. Histone deacetylase inhibition, especially in combination with proteasome inhibition, may be effective acute leukemia treatment. [Copyright &y& Elsevier]

Focuses on the study examined the chronic disease myelocytic leukemia (CML). Historical origin of the disease; Impact of the discovery of the Philadelphia chromosome on CML diagnosis; Pathophysiology of the condition; Analysis on the molecular biology of the t(9;22) translocation.

Focuses on a study which presented the approaches to and molecular monitoring of therapy for chronic myelocytic leukemia (CML). Evolution of the therapeutic approaches for the disease; Effectiveness of the Imatinib therapy as measured by molecular methods; Strategies for the management of CML patients.

Examines the expression of KL-6 antigen messenger RNA on leukemia cells of monocytoid blast crisis in a patient with chronic myelocytic leukemia using a reverse transcriptase-polymerase chain reaction (RT-PCR). Methodology used in the reverse RT-PCR; Application of the immunohistochemical method in determining the localization of KL-6.

Chronic myelocytic leukemia (CML) can occasionally occur after long-term chemotherapy for solid tumors; solid tumors secondary to chemotherapy and biotherapy for CML have also been reported. However, concurrence of these two phenomena in an untreated patient has seldom been reported. Herein, we describe the case of a female patient in her early 60 s who was transferred to the liver surgery department after the discovery of a large liver mass and elevated plasma alpha-fetoprotein levels. She was initially diagnosed with liver cancer. Blood tests indicated an increased platelet count (2464 × 10 9 /L). Chromosomal examination from a bone marrow biopsy indicated the presence of the t(9;22) translocation, and subsequent fluorescence in situ hybridization and PCR were positive for the BCR-ABL rearrangement. A diagnosis of CML was made. The patient received hydroxyurea and imatinib to treat CML and underwent subsequent platelet-lowering therapy and a liver biopsy, which suggested moderately poorly differentiated adenocarcinoma or potentially hepatic metastatic carcinoma. However, the patient refused further pathological examination or screening for the site of the primary tumor. She died 6.5 months after discharge. The exact relationship between the two tumors remains unclear, and more patients need to be evaluated.

Hereditary spherocytosis (HS) and Chronic myelocytic leukemia (CML) are both life threatening hemotologic diseases. They are rarely seen to occur simultaneously in one individual patient. Here we demonstrate a case of HS associated with CML in this study. The patient is a young female, diagnosed with HS in 2005, and was given partial embolization of the splenic artery. She got significant remission after the procedure. In 2008, she was found abnormal in blood routine test, after bone marrow routine, chromosome and fusion gene tests, she was diagnosed with CML (chronic phase). She did not receive regular treatment until 3 months prior, and is currently being treated with Dasatimib. She achieved hematological remission, but had no significant improvement in chromosome and fusion gene figures. Due to her severe condition of hemolysis, a splenectomy or an allogeneic hematopoietic stem cell transplantation is considered. [ABSTRACT FROM AUTHOR]

The osmotic behavior of control lymphocytes (CL) and polymorphonuclears (CPMN) was compared with that of cells from patients with chronic lymphocytic leukemia (CLL) and chronic myelocytic leukemia (CML), using the method of gradual dialysis against distilled water. The results were evaluated with a fragiligraph, and by scanning (SEM) and transmission (TEM) electron microscopy. The fragiligraph curves showed that CLL cells are more resistant to osmotic pressure than the CL, whereas the curves for CPMN and CML cells showed an overlap. Surface alterations in CL appeared as early as 1 min of dialysis, while in CLL cells the membrane did not show major alterations even after 5 min of dialysis. CPMN also showed alterations earlier than CML cells, but this difference was not as prominent as in the case of lymphocytes and was observed for a maximum of 3 min of dialysis. The internal structure of the cells was altered earlier than the surface membrane and this was expressed mainly in the nucleus in both control and leukemic cells. Also in this respect, the internal structure of CL was altered earlier than that of CLL cells, whereas no major differences were observed between CPMN and CML cells. [ABSTRACT FROM AUTHOR]

Nine previously untreated patients with Philadelphia chromosome-positive chronic myelocytic leukemia (CML) were treated with recombinant interferon alpha 2a (rIFN-alpha 2a) and hydroxyurea. Patients received 6×10 U rIFN-alpha 2a daily for the first week and 3×10 U rIFN-alpha 2a daily for the second week. As maintenance treatment starting on day 15, patients received 3×10 U rIFN-alpha 2 a 3 times a week. Simultaneously, hydroxyurea was given, starting at a dose of 40 mg/kg on day one. The maintenance dosage was adjusted to the white blood cell count. Two patients responded with complete hematological remissions but without cytogenetic and molecular-genetic improvements. Seven patients responded with partial hematological remissions. Response to therapy was rapid; normal white blood cell counts were reached after a median of 12 days. The doses of rIFN-alpha 2a and hydroxyurea needed to keep the leucocyte count in the normal range were low (3×10 U rIFN-alpha 2a 3 times per week, 0.5-1.5 g hydroxyurea/day). Acute toxicity of the combination therapy consisted of fever (9 of 9 patients), flulike symptoms (7 of 9 patients), pruritus and/or rash (3 of 9 patients) and evidence of a tumor cell lysis syndrome (1 of 9 patients). The side effects were not dose-limiting. Combination therapy with rIFN-alpha 2a and hydroxyurea for CML is well tolerated and allows quick and effective hematological control of the disease. [ABSTRACT FROM AUTHOR]

We have studied the clinical courses of 69 patients with blastic crises of Philadelphia chromosome positive CML to identify parameters that were associated with an increased response rate or survival. Cytogenetic analysis at the time of blastic transformation revealed additional chromosome changes in 70% of the patients tested. Bone marrow fibrosis was detected in 58% of evaluable patients. Lymphoblastic transformation was seen in 28% of the patients tested with cell surface marker analysis. The value of 5'-nucleotidase as a marker for distinguishing lymphoid from non-lymphoid blast crisis was confirmed. Of 57 evaluable patients, 23 (40%) responded to therapy (CR/PR longer than 14 days). Median survival was 75 days. Longer survival was related to the following factors: Ph-chromosome as the only detectable cytogenetic abnormality; lymphoblastic transformation; no bone marrow fibrosis; high percentage of blasts and promyelocytes in the bone marrow, and response to therapy. No prognostic significance was associated with age, sex, Tdt, LDH, spleen size, duration of the chronic phase of the disease, white blood cell count, Hb, platelet count and percentages of basophils, eosinophils, erythroblasts and blasts and promyelocytes in the peripheral blood. These data confirm the poor prognosis of patients with blastic crisis of CML treated by conventional chemotherapy. [ABSTRACT FROM AUTHOR]

We report on the first Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) characterized by a rearrangement within the 5′ part of the bcr gene on chromosome 22, but outside the restricted breakpoint cluster region. In situ hybridization studies revealed a translocation of the c- abl oncogene to the Ph chromosome and Northern blot analysis identified a chimeric 8 kb bcr/abl RNA transcript in leukemic cells. These data suggest that 1. less bcr coding sequences than previously assumed may be essential for the putative transforming activity of the rearranged bcr/abl gene and 2. the bcr probes currently used for diagnostic purposes could miss Ph-positive CML cases. [ABSTRACT FROM AUTHOR]

A rare case of primary biliary cirrhosis, ulcerative colitis and chronic myelocytic leukemia is described in a 49-year-old Japanese diabetic woman. Primary biliary cirrhosis was diagnosed by characteristic liver histology and positive serum mitochondrial antibody test. Ulcerative colitis was diagnosed by typical findings of barium enema and colonoscopy, negative fecal test for pathogens and compatible rectal histology. Chronic myelocytic leukemia was determined by representative hematologic findings and positive result for Ph chromosome. This is the first case with combination of primary biliary cirrhosis, ulcerative colitis and chronic myelocytic leukemia. [ABSTRACT FROM AUTHOR]

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We report a unique case of chronic myelocytic leukemia (CML) with the Philadelphia (Ph) chromosome. The patient obtained cytogenetic complete remission (CR) after treatment with interferon (IFN). When he transformed to acute lymphocytic leukemia (ALL), cytogenetic analysis showed that the karyotype was normal and fluorescence in situ hybridization (FISH) indicated that blast cells were Ph-negative. Immunophenotyping showed that the cells were CD34-positive and CD38-negative. Blast cells in his final stage were BCR/ABL rearrangement negative by reverse transcription polymerase chain reaction (RT-PCR). [Copyright &y& Elsevier]

Investigates the elevation of serum procalcitonin (PCT) level in a patient with chronic myelocytic leukemia. Measurement of the PCT level using a specific and ultrasensitive immunoluminometric assay; Effect of chemotherapy on the serum PCT and white blood cell count.