Search

Mastocytosis is a neoplasm characterized by a clonal proliferation of mast cells, which accumulate in one or multiple organs, associated with an extremely heterogeneous clinical presentation. The disease can be limited to the skin (cutaneous mastocytosis) that is mostly seen in childhood and usually behaves in a benign fashion. Adult patients most often present with systemic disease with or without skin lesions. This includes indolent forms such as indolent systemic mastocytosis and its subvariant bone marrow mastocytosis, and smoldering systemic mastocytosis as well as aggressive forms including aggressive systemic mastocytosis, systemic mastocytosis with an associated myeloid neoplasm (previously called systemic mastocytosis with an associated hematologic neoplasm), and mast cell leukemia. In addition, mast cell sarcoma is a rare aggressive form of mastocytosis that can present in the skin as well as at extracutaneous sites. This review article focuses on the updates in mastocytosis of the 2022 international consensus classification (ICC)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The role of imatinib in PDGFRA/B-negative hypereosinophilic syndromes (HES) is controversial because of the heterogeneity of HES and the scarcity of prospective studies. We conducted a phase II clinical trial to evaluate the efficacy of imatinib in PDGFRA/B-negative HES. Thirty-two patients were treated with imatinib (100-400 mg daily), and the molecular basis of their response was identified using whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS). The haematological response rate was 46.9%, with a complete haematological response (CHR) rate of 18.8%. The median time to response was 1.5 months. Among the six patients who achieved CHR, five maintained it until the 24th cycle of imatinib and one lost response after 20 months. The median progression-free survival was 4.3 months. WES and WTS were conducted for 11 patients. The number of non-silent mutations did not differ between responders and non-responders. Nine differentially expressed genes, including SNORD15A, were downregulated in responders. STAT5B::RARA, PAK2::PIGX, and FIP1L1::CHIC2 fusions were identified in patients with sustained responses, and RNF130::BRAF and WNK1::KDM5A fusions were identified in non-responders. Imatinib, along with an appropriate biomarker, could be a promising option for PDGFRA/B-negative HES., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Simple Summary: The diagnostic assessment of eosinophilias is complex, requiring a multidisciplinary approach and often involving diagnostic challenges. This work aims for a better understanding of the cytomorphological features, immunophenotype, and biological activity of the eosinophil. Additionally, the concepts of peripheral and bone marrow eosinophilia and their potential causes are reviewed. Finally, the review focuses on the broad differential diagnosis of hematologic diseases that may underlie eosinophilia and how to diagnose them. Among the findings that should raise suspicion of hematologic diseases associated with eosinophilia are the presence of splenomegaly and/or lymphadenopathy or an abnormal blood count. In recent years, with advances in molecular techniques, new hematologic malignancies such as myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions are being defined, where eosinophilia can serve as a guiding sign. In these cases, an accurate diagnosis allows for the use of targeted therapy with an improvement in the quality of life and survival of patients. Eosinophils in peripheral blood account for 0.3–5% of leukocytes, which is equivalent to 0.05–0.5 × 109/L. A count above 0.5 × 109/L is considered to indicate eosinophilia, while a count equal to or above 1.5 × 109/L is defined as hypereosinophilia. In bone marrow aspirate, eosinophilia is considered when eosinophils make up more than 6% of the total nuclear cells. In daily clinical practice, the most common causes of reactive eosinophilia are non-hematologic, whether they are non-neoplastic (allergic diseases, drugs, infections, or immunological diseases) or neoplastic (solid tumors). Eosinophilia that is associated with a hematological malignancy may be reactive or secondary to the production of eosinophilopoietic cytokines, and this is mainly seen in lymphoid neoplasms (Hodgkin lymphoma, mature T-cell neoplasms, lymphocytic variant of hypereosinophilic syndrome, and B-acute lymphoblastic leukemia/lymphoma). Eosinophilia that is associated with a hematological malignancy may also be neoplastic or primary, derived from the malignant clone, usually in myeloid neoplasms or with its origin in stem cells (myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions, acute myeloid leukemia with core binding factor translocations, mastocytosis, myeloproliferative neoplasms, myelodysplastic/myeloproliferative neoplasms, and myelodysplastic neoplasms). There are no concrete data in standardized cytological and cytometric procedures that could predict whether eosinophilia is reactive or clonal. The verification is usually indirect, based on the categorization of the accompanying hematologic malignancy. This review focuses on the broad differential diagnosis of hematological malignancies with eosinophilia. [ABSTRACT FROM AUTHOR]

Systemic mastocytosis is defined by the clonal proliferation of abnormal mast cells. The clinical course can range from indolent forms with normal life expectancy to advanced mast cell leukemia with dismal prognosis. An association with other diseases, including myeloproliferative neoplasia, has been described. We present a case of a 75-year patient with a history of cutaneous mastocytosis who was diagnosed with mast cell leukemia more than 9 years ago and did not receive treatment. The patient presented to our clinic with acute kidney failure because of renal extramedullary hematopoiesis. Bone marrow histopathology revealed extensive fibrosis and 50% infiltration by mast cells with a c-KIT D816V mutation. No mutations supporting primary myelofibrosis were identified. Treatment with midostaurin was started, and the patient was discharged after improvement of renal function. Here, we discuss diagnostic challenges between different forms of mast cell leukemia and overlaps with other hematological malignancies. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Hematology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: Many patients with chronic-phase chronic myeloid leukemia (CP-CML) treated with a tyrosine kinase inhibitor (TKI) experience disease progression and switch to another TKI, but each switch yields diminishing returns. To gain insight into the burden of repeated TKI treatment failures, this study analyzed the characteristics, treatment and disease patterns, and outcomes of adult patients with CP-CML in France whose disease progressed after treatment with two or more TKIs between 2006 and 2021. Patients switched TKIs up to six times; in many cases, treatment with the first and second TKIs lasted <2 years. On the other hand, patients who showed a good response to their third TKI had a lower risk of death. These findings provide a broad view of CP-CML treatment in France over the last 15 years and highlight the need for more effective therapies early in the treatment course that can improve outcomes for patients with CP-CML. This retrospective chart review study investigated the clinical burden of adult patients with chronic-phase chronic myeloid leukemia (CP-CML) treated at three centers in France (2006–2021) who failed on two or more tyrosine kinase inhibitors (TKIs; third-line [3L]+ cohort) or harbored the BCR::ABL1 T315I mutation (T315I cohort). In the 3L+ cohort (N = 157; median age at diagnosis, 56 years), TKIs received in 3L (median duration: 17 months) were dasatinib (32%), nilotinib (19%), imatinib (18%), ponatinib (17%), and bosutinib (14%). Of the 145 patients with documented responses in 3L, 42% experienced major molecular response (MMR) at 12 months. Median event-free survival [95% confidence interval] was 53.6 [44.0, 67.5] months, and median progression-free survival and overall survival (OS) were not reached. Achieving MMR in 3L was associated with a decreased mortality risk. In the T315I cohort (N = 17; 52 years), 41% of patients received five or more lines of therapy. Following identification of the T315I mutation, ponatinib was the most common TKI used (59%); the median [interquartile range] OS was 5 [3–10] years. The most common adverse events were infections (3L+ cohort) and thrombocytopenia (T315I cohort) (both 18%). Well-tolerated therapies that achieve durable responses are needed in 3L or earlier to improve CP-CML prognosis. [ABSTRACT FROM AUTHOR]

Introduction. MicroRNA (miR) 155 has been implicated in the regulation of innate and adaptive immunity as well as antiviral responses, but its role during respiratory syncytial virus (RSV) infections is not known. The objective of this study was to investigate the expression of miR-155 using pharyngeal swabs and peripheral blood in infants with RSV infection and uninfected controls. Methods. A prospective age-matched study was conducted in primary care in Torino from 1 August 2018 to 31 January 2020. We enrolled 66 subjects, 29 of them patients with RSV infection and 37 age-matched uninfected controls, and collected pharyngeal swabs and peripheral blood in order to assess miR-155 expression with real-time stem–loop–TaqMan real-time PCR. Results. The data show that there is no correlation between pharyngeal swabs and peripheral blood with respect to miR-155 expression. The 1/ΔCq miR-155 expression levels in throat swabs in RSV bronchiolitis patients and healthy controls were 0.19 ± 0.11 and 0.21 ± 0.09, respectively, and were not significantly different between healthy controls and bronchiolitis (p = 0.8414). In the peripheral blood, miR-155 levels were higher than those of healthy control subjects: 0.1 ± 0.013 and 0.09 ± 0.0007, respectively; p = 0.0002. Discussion. Our data provide evidence that miR-155 expression is higher in peripheral blood during RSV infection but not in swabs. This difference in the timing of sample recruitment could explain the differences obtained in the results; miR-155 activation is probably only assessable in the very early stages of infection in the swab and remains visible for longer in the blood. New investigations are needed in order to clarify whether the miR-155 expression in swabs can be influenced by different stages of virus disease of infants. [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia (CML) management during pregnancy is challenging. In this retrospective study, hospital records of CML patients treated between 2000 and 2021 were screened to identify patients who tried to conceive/got pregnant (planned and unplanned) on TKIs (tyrosine kinase inhibitors)/were pregnant at CML onset/fathered a child. We found ninety-three pregnancies involving thirty-three women and thirty-eight men, and they were analyzed for the pregnancy outcomes and the strategies utilized for CML management during pregnancy and the pre-conception period. There were two women and four men with primary infertility and five women with secondary infertility. TKIs were discontinued before conception in four planned pregnancies and at the time of recognition of pregnancy in unplanned pregnancies (n = 21). Unplanned pregnancy outcomes were two miscarriages, eight elective terminations, and eleven live births. Planned pregnancies led to four healthy babies. Outcomes of pregnancies at CML onset (n = 17) were six live births, one stillbirth, five elective terminations, and five abortions. Except for one child with congenital micro-ophthalmia, no other child born to the women on TKI had any malformations. Thirty-eight men fathered 51 healthy children. All but two patients (one planned and one unplanned pregnancy) lost their hematological responses during pregnancy and gained their previous best response after restarting TKI. In women who were pregnant at CML onset, complete cytological remission (CCYR) was achieved between 7 and 24 months (median:14 months) after starting TKI. During pregnancy, intermittent hydroxyurea ± TKI (in the second and third trimesters) was used to keep WBCs less than 30,000/mm3. Outcomes of pregnancies in CML patients can be optimized with our approach. TKIs (Imatinib and Nilotinib) can be safely used in the second and third trimesters. Delayed initiation or interruption of TKI during pregnancy does not negatively affect response to TKIs. [ABSTRACT FROM AUTHOR]

The imatinib-sensitive fusion gene FIP1L1::PDGFRA is the most frequent molecular abnormality identified in patients with eosinophilic myeloid neoplasms. Rapid recognition of this mutation is essential given the poor prognosis of PDGFRA-associated myeloid neoplasms prior to the availability of imatinib therapy. We report a case of a patient in whom delayed diagnosis resulted in cardiac transplantation for eosinophilic endomyocardial fibrosis. The delay in diagnosis was due, in part, to a false-negative result in fluorescence in situ hybridization (FISH) testing for FIP1L1::PDGFRA. To explore this further, we examined our cohort of patients presenting with confirmed or suspected eosinophilic myeloid neoplasms and found 8 additional patients with negative FISH results despite a positive reverse-transcriptase polymerase chain reaction test for FIP1L1::PDGFRA. More importantly, false-negative FISH results delayed the median time to imatinib treatment by 257 days. These data emphasize the importance of empiric imatinib therapy in patients with clinical features suggestive of PDGFRA-associated disease. [ABSTRACT FROM AUTHOR]

The introduction of tyrosine kinase inhibitors (TKIs) has changed the treatment paradigm of chronic myeloid leukemia (CML), leading to a dramatic improvement of the outcome of CML patients, who now have a nearly normal life expectancy and, in some selected cases, the possibility of aiming for the more ambitious goal of treatment-free remission (TFR). However, the minority of patients who fail treatment and progress from chronic phase (CP) to accelerated phase (AP) and blast phase (BP) still have a relatively poor prognosis. The identification of predictive elements enabling a prompt recognition of patients at higher risk of progression still remains among the priorities in the field of CML management. Currently, the baseline risk is assessed using simple clinical and hematologic parameters, other than evaluating the presence of additional chromosomal abnormalities (ACAs), especially those at "high-risk". Beyond the onset, a re-evaluation of the risk status is mandatory, monitoring the response to TKI treatment. Moreover, novel critical insights are emerging into the role of genomic factors, present at diagnosis or evolving on therapy. This review presents the current knowledge regarding prognostic factors in CML and their potential role for an improved risk classification and a subsequent enhancement of therapeutic decisions and disease management. [ABSTRACT FROM AUTHOR]

Narrow-band UVB phototherapy and psoralen-ultraviolet a photochemotherapy in the treatment of cutaneous mastocytosis: a study in 20 patients. 14 Prignano F, Troiano M, Lotti T. Cutaneous mastocytosis: successful treatment with narrowband ultraviolet B phototherapy. A case of pediatric indolent systemic mastocytosis: The role of UVB-NB phototherapy in the treatment of cutaneous lesions. [Extracted from the article]

Chronic myeloid leukemia (CML) is a malignant hematopoietic stem cell disease resulting in the fusion of BCR and ABL genes and characterized by the presence of the reciprocal translocation t(9;22)(q34;q11). BCR-ABL, a product of the BCR-ABL fusion gene, is a structurally active tyrosine kinase and plays an important role in CML disease pathogenesis. Imatinib mesylate (IMA) is a strong and selective BCR-ABL tyrosine kinase inhibitor. Although IMA therapy is an effective treatment, patients may develop resistance to IMA therapy over time. This study investigated the possible genetic resistance mechanisms in patients developing resistance to IMA. We did DNA sequencing in order to detect BCR-ABL mutations, which are responsible for IMA resistance. Moreover, we analyzed the mRNA expression levels of genes responsible for apoptosis, such as BCL-2, P53, and other genes (SCD-1, PTEN). In a group of CML patients resistant to IMA, when compared with IMA-sensitive CML patients, a decrease in SCD-1 gene expression levels and an increase in BCL-2 gene expression levels was observed. In this case, the SCD-1 gene was thought to act as a tumor suppressor. The present study aimed to investigate the mechanisms involved in IMA resistance in CML patients and determine new targets that can be beneficial in choosing the effective treatment. Finally, the study suggests that the SCD-1 and BCL-2 genes may be mechanisms responsible for resistance. [ABSTRACT FROM AUTHOR]

Mastocytosis is a neoplasm characterized by a clonal proliferation of mast cells, which accumulate in one or multiple organs, associated with an extremely heterogeneous clinical presentation. The disease can be limited to the skin (cutaneous mastocytosis) that is mostly seen in childhood and usually behaves in a benign fashion. Adult patients most often present with systemic disease with or without skin lesions. This includes indolent forms such as indolent systemic mastocytosis and its subvariant bone marrow mastocytosis, and smoldering systemic mastocytosis as well as aggressive forms including aggressive systemic mastocytosis, systemic mastocytosis with an associated myeloid neoplasm (previously called systemic mastocytosis with an associated hematologic neoplasm), and mast cell leukemia. In addition, mast cell sarcoma is a rare aggressive form of mastocytosis that can present in the skin as well as at extracutaneous sites. This review article focuses on the updates in mastocytosis of the 2022 international consensus classification (ICC). [ABSTRACT FROM AUTHOR]

Chronic eosinophilic leukemia (CEL) is a rare chronic myeloproliferative disorder characterized by sustained eosinophilia. Although the incidence of CEL is uncertain, it can be clinically devastating as it has a propensity to affect several important organ systems. This is of particular significance in Sub-Saharan Africa where helminthic infections are a more prevalent cause of eosinophilia. To the best of our knowledge, we present the first reported case of CEL complicated by cardiac disease in a Ghanaian. He presented with a history of orthopnoea and dyspnoea on exertion, and examination revealed a pansystolic murmur over the mitral region and moderate splenomegaly. Good symptomatic control was achieved using hydroxyurea after which haematologic and cytogenetic remission was achieved after 12 weeks on a tyrosine kinase inhibitor. Physicians working in low resource environments should exclude clonality in patients presenting with eosinophilia and end-organ damage. [ABSTRACT FROM AUTHOR]

Copyright of Turkderm - Turkish Archives of Dermatology & Venereology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Intestinal dysfunction is a common complication of acute pancreatitis. MiR155 may be involved in the occurrence and development of intestinal dysfunction mediated by acute pancreatitis, but the specific mechanism is not clear. Aims: To investigate the effect of miR155 on severe acute pancreatitis (SAP)-associated intestinal dysfunction and its possible mechanism in a mice model. Methods: In this study, SAP mice model was induced by intraperitoneal injection of caerulein and LPS in combination. Adeno-associated virus (AAV) was given by tail vein injection before the SAP model. The pancreatic and intestinal histopathology changes were analyzed. Cecal tissue was collected for 16S rRNA Gene Sequencing. Intestinal barrier proteins ZO-1 and E-cad were measured by Immunohistochemistry Staining and Western Blot, respectively. Intestinal tissue miR155 and inflammatory factors TNF-α, IL-1β, and IL-6 were detected by Q-PCR. The expression levels of protein associated with TNF-α and TLR4/MYD88 pathway in the intestinal were detected. Results: In miR155 overexpression SAP group, the levels of tissue inflammatory factor were significantly increased, intestinal barrier proteins were significantly decreased, and the injury of intestinal was aggravated. Bacterial 16S rRNA sequencing was performed, showing miR155 promotes gut microbiota dysbiosis. The levels of TNF-α, TLR4, and MYD88 in the intestinal were detected, suggesting that miR155 may regulate gut microbiota and activate the TLR4/MYD88 pathway, thereby affecting the release of inflammatory mediators and regulating SAP-related intestinal injury. After application of miR155-sponge, imbalance of intestinal flora and destruction of intestinal barrier-related proteins have been alleviated. The release of inflammatory mediators decreased, and the histopathology injury of intestinal was improved obviously. Conclusion: MiR155 may play an important role in SAP-associated intestinal dysfunction. MiR155 can significantly alter the intestinal microecology, aggravated intestinal inflammation through TLR4/MYD88 pathway, and disrupts the intestinal barrier in SAP mice. [ABSTRACT FROM AUTHOR]

Simple Summary: K14-HPV16 transgenic mice have proved to be a useful model to study the carcinogenic cascade induced by HPV16, the tumor microenvironment and also the epigenetic and genetic factors associated with this type of malignancy. The aim of our study was to evaluate the infiltration of mast cells in two cutaneous regions with different severity of the lesions and to identify potential microRNAs that may regulate mast cell infiltration in this model. We were able to confirm that increased mast cell infiltration is associated with progression of HPV-induced lesions, and that miR-223-3p and miR-125b-5p might be assisting this process via the regulation of mast cell chemotactic proteins. High-risk human papillomavirus (HPV) is the etiologic agent of several types of cancer. Mast cells' role as either a driving or opposing force for cancer progression remains controversial. MicroRNAs are dysregulated in several HPV-induced cancers, and can influence mast cell biology. The aim of this study was to evaluate mast cell infiltration and to identify microRNAs potentially regulating this process. Transgenic male mice (K14-HPV16; HPV+) and matched wild-type mice (HPV−) received 7,12-Dimethylbenz[a]anthracene (DMBA) (or vehicle) over 17 weeks. Following euthanasia, chest skin and ear tissue samples were collected. Mast cell infiltration was evaluated by immunohistochemistry. MicroRNAs associated with mast cell infiltration were identified using bioinformatic tools. MicroRNA and mRNA relative expression was evaluated by RT-qPCR. Immunohistochemistry showed increased mast cell infiltration in HPV+ mice (p < 0.001). DMBA did not have any statistically significant influence on this distribution. Ear tissue of HPV+ mice showed increased mast cell infiltration (p < 0.01) when compared with chest skin samples. Additionally, reduced relative expression of miR-125b-5p (p = 0.008, 2−ΔΔCt = 2.09) and miR-223-3p (p = 0.013, 2−ΔΔCt = 4.42) seems to be associated with mast cell infiltration and increased expression of target gene Cxcl10. These results indicate that HPV16 may increase mast cell infiltration by down-regulating miR-223-3p and miR-125b-5p. [ABSTRACT FROM AUTHOR]

To explore the genetic and clinical features of a rare t(1;12)(q21;p13) in a patient with myelodysplastic syndrome (MDS). A 53‐year‐old male was diagnosed as high‐risk MDS, and died in a short period. A complete cytogenetic analysis of bone marrow by conventional G‐banding karyotyping was performed at the time of initial evaluation. On the basis of chromosome karyotype, interphase and metaphase fluorescence in‐situ hybridization (FISH) were carried out to further confirm the abnormal karyotypes. Reverse‐transcription polymerase chain reaction (RT‐PCR) was performed to determine ETV6/ARNT fusion gene status. G‐banding revealed karyotype 47, XY, +8, der(12) t(1;12)(q21;p13). FISH with the centromere 8 probe verified the trisomy 8, and the ETV 6 break‐apart probe suggested heterozygous loss of ETV6 allele located in short arm of chromosome 12. Subsequently, the painting probe of whole chromosome 12 further confirmed the part break of short arm of chromosome 12, and the 1q21/1p36 probe yielded three signals of 1q21 and two signals of 1p36. The results of FISH were in accordance with the karyotype completely. No ETV6/ARNT fusion gene was detected by PCR. T(1;12)(q21;p13) is a rare abnormal karyotype, and the limited reports cannot supply definite clinical significance. Rapid deterioration of our case suggests this translocation of chromosome might have a poor effect on the survival of MDS. [ABSTRACT FROM AUTHOR]

Diagnostic tests can detect diseases, monitor responses, and inform treatments. They are vital to the effective management of disease. There have been significant advances in the engineering of new diagnostic technologies. These technologies may forgo sample extraction, simplify readout, or automate processing. Many researchers design these diagnostics based on test performance in a limited sample subset. This approach ignores the intertwined relationship between patient characteristics and diagnostic test results. Yet, it is important to understand the clinical decision‐making workflow and how the disease manifests in order to optimally design diagnostic tests. This review article explores the three aspects of incorporating patient characteristics to maximize diagnostic performance. 1) Characterize patient populations using patient demographics, disease prevalence, and other unique features. 2) Use the characteristics of the patient population to establish design requirements. 3) Determine the best use case since each case has different performance and target requirements. In this framework the clinical, technological, and unmet needs of a patient population shape the diagnostics design requirements. Following these steps will lead to maximal diagnostic performance and poise new diagnostics for real world use. [ABSTRACT FROM AUTHOR]

Background: Gastric diffuse large B‐cell lymphoma (DLBCL) is often associated with Helicobacter pylori (H. pylori) infection. Those in the early stage could be treated with H. pylori eradication therapy, and are classified into a sensitive group and a resistant group. Methods: Genome‐wide miRNA and miRNA expression profiles were obtained from biopsy specimens of gastric DLBCL. MiRNAs and their targets as predictors of responses to H. pylori eradication therapy were identified through differential expression and pathway enrichment analysis, and further confirmed with transfection experiments in lymphoma cell lines of B‐cell origin. Results: Genome‐wide miRNA and mRNA profiles showed miR‐200 was associated with the sensitive group, and that the resistant group had higher levels of miR‐155 and lower levels of DEPTOR (an inhibitor of mTOR) than the sensitive group. BJAB cells transfected with miR‐155 also had lower DEPTOR and higher mTOR levels. Therefore, miR‐155‐mediated inhibition of DEPTOR with secondary activation of mTOR was a potential marker for resistance to H. pylori eradication therapy. In contrast, pathway enrichment analysis showed that Toll‐like receptor 5 (TLR5), the receptor for bacterial flagellin, was a potential marker for sensitivity to H. pylori eradication therapy. In an independent series, stronger expression of pS6K1 (a direct target of mTOR) was associated with the resistant group and morphologic evidence of active gastritis was associated with the sensitive group. Conclusions: These findings showed that activation of the miR‐155‐DEPTOR pathway is a marker for resistance to H. pylori eradication therapy, and that histological evaluation of active gastritis might be used as a surrogate marker to predict responses to H. pylori eradication therapy in gastric DLBCL. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) form a sentinel network to induce protective immunity against pathogens or self-tolerance. mRNA stability is an important part of the post-transcriptional regulation (PTR) that controls the maturation and function of DCs. In this review, we summarize the effects of TTP-mediated regulation of mRNA stability in DCs, focusing on DC maturation and antigen presentation, T cell activation and differentiation, immune tolerance and inflammation. We also discuss the potential DC-based immune treatment for HIV+ patients through regulation of mRNA stability. This review proposes the regulation of mRNA stability as a novel immune therapy for various inflammatory diseases, such as arthritis and dermatitis. [ABSTRACT FROM AUTHOR]

Systemic mastocytosis (SM) comprises a group of rare disorders resulting from tissue infiltration by pathological mast cells. In a percentage ranging from 5 to 40% in various patient series, SM appears to be associated with an accompanying hematologic neoplasm (SM-AHN). The coexistence of SM with chronic myelogenous leukemia (CML) is extremely rare with only 3 cases in the literature. The natural course of CML has changed dramatically over the past 2 decades with the use of tyrosine kinase inhibitors (TKIs). We report a case of diagnosing SM in a patient in complete molecular remission of CML after stopping TKI treatment. [ABSTRACT FROM AUTHOR]

Systemic mastocytosis (SM) is a rare neoplasm resulting from extracutaneous infiltration of clonal mast cells (MC). The clinical features of SM are very heterogenous and treatment should be highly individualized. Up to 40% of all SM cases can be associated with another hematological neoplasm, most frequently myeloproliferative neoplasms. Here, we present a patient with indolent SM who subsequently developed a myeloid neoplasm with PDGFRA rearrangement with complete response to low-dose imatinib. The 63-year-old patient presented with eosinophilia and elevated serum tryptase level. Bone marrow analysis revealed aberrant MCs in aggregates co-expressing CD2/CD25 and KIT D816V mutation (0.01%), and the FIP1L1-PDGFRA fusion gene was not identified. In the absence of 'B' and 'C' findings, we diagnosed an indolent form of SM. For 2 years after the diagnosis, the absolute eosinophil count progressively increased. Bone marrow evaluation showed myeloid hyperplasia and the FIP1L1-PDGFRA fusion gene was detected. Thus, the diagnosis of myeloid neoplasm with PDGFRA rearrangement was established. The patient was treated with imatinib 100 mg daily and rapidly obtained a complete molecular remission. The clinical, biological, and therapeutic aspects of SM might be challenging, especially when another associated hematological disease is diagnosed. Little is known about the underlying molecular and immunological mechanisms that can promote one entity prevailing over the other one. Currently, the preferred concept of SM pathogenesis is a multimutated neoplasm in which KIT mutations represent a "phenotype modifier" toward SM. Our patient showed an evolution from KIT mutated indolent SM to a myeloid neoplasm with PDGFRA rearrangement; when the eosinophilic component expanded, a regression of the MC counterpart was observed. In conclusion, extensive clinical monitoring associated with molecular testing is essential to better define these rare diseases and consequently their prognosis and treatment. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency and clinico-haematological features of PDGFRA, PDGFRB and FGFR1 gene rearrangements in patients with persistent Eosinophilia using Fluorescence in situ hybridization. Study Design: Cross-sectional study. Place and Duration of Study: Department of Hematology, Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Dec 2018 to Dec 2019. Methodology: All Patients who presented to AFIP having absolute eosinophil count >1.5x109/L persistent for over six months or with Myeloid or Lymphoid neoplasms with persistent Eosinophilia were studied. Patients having reactive Eosinophilia and those on treatment were excluded. Interphase FISH studies were performed. In addition, 2.5ml of sodium heparin blood was taken. After the denaturation of DNA, slides were set up according to standard protocol. FIP1L1/CHIC2/PDGFRA dual colour probe was applied for PDGFRA, 5q32 PDGFRA break apart probe for PDGFRB and XL FGFR1 break apart probe for FGFR1 gene rearrangement. Results: A total of 60 patients were included in the study. Of these, 50(83.3%) were males, and 10(16.7%) were females, with an average absolute Eosinophilia count of 5.92±7.10x109/L. The only rearrangement detected in patients with Eosinophilia was FIPILI-PDGFRA gene fusion, detected in 20% of the patients. No other rearrangement was found. Conclusion: PDGFRA, PDGFRB and FGFR1 mutations are rare yet most prominent in patients with clonal Eosinophilia. About 80% of eosinophilic patients were found to have idiopathic Eosinophilia, which requires further consideration to address the disease prevalence. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors declare no conflict of interest.

Chronic Myeloid Leukemia (CML) is a rare malignant proliferative disease of the hematopoietic system, whose molecular hallmark is the Philadelphia chromosome (Ph). The Ph chromosome originates an aberrant fusion gene with abnormal kinase activity, leading to the buildup of reactive oxygen species and genetic instability of relevance in disease progression. Several genetic abnormalities have been correlated with CML in the blast phase, including chromosomal aberrations and common altered genes. Some of these genes are involved in the regulation of cell apoptosis and proliferation, such as the epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), or Schmidt-Ruppin A-2 proto-oncogene (SRC); cell adhesion, e.g., catenin beta 1 (CTNNB1); or genes associated to TGF-β, such as SKI like proto-oncogene (SKIL), transforming growth factor beta 1 (TGFB1) or transforming growth factor beta 2 (TGFB2); and TNF-α pathways, such as Tumor necrosis factor (TNFA) or Nuclear factor kappa B subunit 1 (NFKB1). The involvement of miRNAs in CML is also gaining momentum, where dysregulation of some critical miRNAs, such as miRNA-451 and miRNA-21, which have been associated to the molecular modulation of pathogenesis, progression of disease states, and response to therapeutics. In this review, the most relevant genomic alterations found in CML will be addressed. [ABSTRACT FROM AUTHOR]