^
9h
Long-term Study Evaluating the Effect of Givinostat in Patients With Chronic Myeloproliferative Neoplasms (clinicaltrials.gov)
P2, N=90, Active, not recruiting, Italfarmaco | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Jun 2025 --> Dec 2026
Trial completion date • Trial primary completion date
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JAK2 (Janus kinase 2)
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Duvyzat (givinostat)
23d
Recombinant interferon alfa in BCR/ABL-negative chronic myeloproliferative neoplasms. (PubMed, Clin Adv Hematol Oncol)
Recent regulatory approvals in polycythemia vera (PV) include the JAK inhibitor ruxolitinib, and more recently, a novel recombinant interferon alfa-2 (IFN-α) therapeutic agent. More recently, a novel pegylated IFN-α, ropeginterferon alfa-2b, received approval for PV by the European Medicines Agency and the US Food and Drug Administration in 2019 and 2021, respectively. This article reviews the clinical research and recent advances that led to the first regulatory approval of IFN-α in a BCR/ABL-negative MPN and its future promise as a disease-modifying therapeutic agent.
Review • Journal
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JAK2 (Janus kinase 2) • CALR (Calreticulin) • IFNA1 (Interferon Alpha 1)
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Jakafi (ruxolitinib) • Besremi (ropeginterferon alfa-2b)
1m
Infrequent Presentations of Chronic NPM1-Mutated Myeloid Neoplasms: Clinicopathological Features of Eight Cases from a Single Institution and Review of the Literature. (PubMed, Cancers (Basel))
Tailoring patient management on an individualized basis, favoring intensive treatment aligned with AML protocols, is crucial, regardless of blast percentage. Research on the impact of NPM1 mutations in non-acute myeloid neoplasms is ongoing, requiring challenging prospective studies with substantial patient cohorts and extended follow-up periods for validation.
Review • Journal
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NPM1 (Nucleophosmin 1)
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NPM1 mutation
1m
Trial completion
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HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1)
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Promune (agatolimod)
2ms
Co-occurrence of JAK2-V617 F mutation and BCR::ABL1 translocation in chronic myeloproliferative neoplasms: a potentially confounding genetic combination. (PubMed, Front Oncol)
Starting from the presentation of two additional cases from our routine daily practice, we focus mainly on clinical, laboratory, and bone marrow histological findings, which may represent useful clues of BCR::ABL1 and JAK2 co-occurrence. The interaction between JAK2 and BCR::ABL1 clones during the disease course as well as therapy and outcome are presented.
Review • Journal
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ABL1 (ABL proto-oncogene 1) • JAK2 (Janus kinase 2) • CALR (Calreticulin)
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JAK2 mutation • CALR mutation
3ms
NCI-2018-03465: Azacitidine, Venetoclax, and Pevonedistat in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov)
P1/2, N=40, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
Trial completion date • Trial primary completion date
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • NPM1 (Nucleophosmin 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
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NPM1 mutation • CEBPA mutation • PDGFRA rearrangement
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Venclexta (venetoclax) • azacitidine • pevonedistat (MLN4924)
3ms
Outcomes of intensive and nonintensive blast-reduction strategies in accelerated and blast-phase MPN. (PubMed, Blood Adv)
Similar overall best response rates were observed in patients receiving induction with daunorubicin combined with cytarabine arabinoside (daunorubicin + ara-C) (74% [23/31]) or FLAG-IDA/NOVE-HiDAC (78% [39/50], p=0.78)...Mutations in TP53 (OR 8.2 [95% CI 2.01, 37.1], p=0.004) and RAS pathway (OR 5.1 [95%CI 1.2, 23.7], p=0.03) were associated with inferior treatment response for intensively-treated patients, and poorer performance status (ECOG) was associated with inferior treatment response in both intensively- (OR 10.4 [95%CI 2.0, 78.5], p=0.009) and nonintensively-treated groups (OR 12 [95%CI 2.04, 230.3], p=0.02). In patients with paired samples prior to and after therapy (N=26), there was a significant residual mutation burden remaining irrespective of response to blast-reduction therapy.
Journal • Tumor mutational burden
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1)
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TP53 mutation
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daunorubicin
3ms
JAK2, CALR, and MPL Mutation Profiles in Colombian patients with BCR-ABL Negative Myeloproliferative Neoplasms. (PubMed, Colomb Med (Cali))
Regarding the hematological results for the mutations, significant differences were found in the hemoglobin level, hematocrit level, and platelet count among the three neoplasms. Thus, this study demonstrates the importance of the molecular characterization of the JAK2, CALR and MPL mutations in Colombian patients (the genetic context of which remains unclear in the abovementioned neoplasms) to achieve an accurate diagnosis, a good prognosis, adequate management, and patient survival.
Journal
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • JAK2 (Janus kinase 2) • CALR (Calreticulin)
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JAK2 V617F • CALR mutation
4ms
JAK2 R683S Mutation Resulting in Dual Diagnoses of Chronic Eosinophilic Leukemia and Myelodysplastic/Myeloproliferative Overlap Syndrome. (PubMed, J Natl Compr Canc Netw)
Although the patient's blood counts initially responded to ruxolitinib and hydroxyurea, the response was not durable. Early referral for allogenic bone marrow transplant appears necessary to prevent long-term complications and disease progression in myeloid neoplasms with clonal hypereosinophilia driven by noncanonical JAK2 mutations.
Journal
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JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1)
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SF3B1 mutation • JAK2 mutation
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Jakafi (ruxolitinib) • hydroxyurea
4ms
High cell-free DNA is associated with disease progression, inflammasome activation and elevated levels of inflammasome-related cytokine IL-18 in patients with myelofibrosis. (PubMed, Front Immunol)
The close correlation shown between IL-18 and cfDNA levels, together with the finding of enhanced DNA-triggered IL-18 release from monocytes, suggest that cfDNA promotes inflammation, at least in part, through inflammasome activation. This work highlights cfDNA, the inflammasome and IL-18 as additional players in the complex inflammatory circuit that fosters MF progression, potentially providing new therapeutic targets.
Journal
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JAK2 (Janus kinase 2) • IL18 (Interleukin 18) • CALR (Calreticulin) • IL1B (Interleukin 1, beta) • NLRP3 (NLR Family Pyrin Domain Containing 3)
4ms
Retrospective Real-World Analysis of Baseline Characteristics and Posttreatment Hematologic Outcomes in Patients with Myelofibrosis Receiving Ruxolitinib (ASH 2023)
This retrospective analysis provides insights into hematologic outcomes under the current first-line treatment paradigm for MF in clinical practice. Many pts who initiated RUX were anemic and/or thrombocytopenic at baseline, and incidences of anemia and thrombocytopenia as well as RBC transfusion burden increased over time. These results highlight the continued need for treatments that address the underlying hematologic burden, including anemia and thrombocytopenia, of pts with MF.
Retrospective data • Real-world evidence • Real-world
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Jakafi (ruxolitinib)
4ms
Performance and Interlaboratory Reproducibility of Droplet Digital Polymerase Chain Reaction (ddPCR) and Real Time PCR for KIT D816V Mutation Detection: A Nationwide Pilot Study By the RIMA (Rete Italiana Mastocitosi) Association (ASH 2023)
Involvement of additional Italian labs is already planned, and further implementation within the ECNM will be proposed. Definition of common SOPs, uniform sample requirements and web-based reporting following the GIMEMA LabNet model will be pursued.
Clinical • Polymerase Chain Reaction
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KIT (KIT proto-oncogene, receptor tyrosine kinase)
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KIT mutation • KIT D816V
4ms
Risk Factors for Thrombosis in Essential Thrombocythemia: A Clinico-Pathological Study of 138 Patents in a Middle Eastern Population (ASH 2023)
Our ET patient population had high prevalence of MPL (Pro106Leu) mutation which may be germ line in nature as previously reported, and correspondingly lowered the prevalence of JAK2V617F and CALR mutations in our cohort. Thrombosis developed in 26. 8% patients.
Clinical
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JAK2 (Janus kinase 2) • CALR (Calreticulin)
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JAK2 V617F • JAK2 mutation • CALR mutation
4ms
A Phase 3b, Randomized, Open-Label, Parallel Group, Multicenter Study to Assess Efficacy, Safety, and Tolerability of Two Dosing Regimens of Ropeginterferon Alfa-2b-Njft (P1101) in Adult Patients with Polycythemia Vera (ASH 2023)
Most patients with PV receive phlebotomy and low-dose aspirin to prevent thrombosis...Treatment-naïve patients and those pretreated with hydroxyurea (HU) will be included...General statistical summaries will be applied to primary and secondary endpoints. For categorical variables, frequency and percentage will be presented with a 95% confidence interval.
Clinical • P3 data
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hydroxyurea • Besremi (ropeginterferon alfa-2b)
4ms
T cell phenotype and lack of eosinophilia are not uncommon in extramedullary myeloid/lymphoid neoplasms with ETV6::FLT3 fusion: a case report and review of the literature. (PubMed, Virchows Arch)
Here, we report a very unusual case of myeloid/lymphoid neoplasm with ETV6::FLT3 fusion with a nodal presentation without associated eosinophilia. Our case draws attention to diagnostic pitfalls in these rare entities.
Review • Journal
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FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • JAK2 (Janus kinase 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ETV6 (ETS Variant Transcription Factor 6)
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FGFR1 fusion • ABL1 fusion • ETV6-ABL1 fusion
5ms
Molecular landscape of the JAK2 gene in chronic myeloproliferative neoplasm patients from the state of Amazonas, Brazil. (PubMed, Biomed Rep)
Thus, individuals with high JAK2V617F variant allele frequency (≥50% VAF) presented more thrombo-hemorrhagic events and manifestations of splenomegaly compared with those with low JAK2V617F variant allele frequency (1 variant in the JAK2 gene, especially rs2230722, rs2230724, and rs77375493 variants, and those with high JAK2V617F VAF show alterations in the clinical-laboratory profile compared with those with low JAK2V617F VAF.
Journal
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ABL1 (ABL proto-oncogene 1) • JAK2 (Janus kinase 2)
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JAK2 V617F
5ms
Chronic neutrophilic leukemia/chronic eosinophilic leukemia (PubMed, Rinsho Ketsueki)
Ruxolitinib, a JAK2 inhibitor, provided a promising therapeutic effect in a phase II study...Anti-CD52 antibody, alemtuzumab, or anti-IL-5 antibody, mepolizumab, are promising drugs to control symptoms that are associated with hypereosinophilic syndrome. Allo-SCT is anticipated as a curative treatment for CEL, but the evidence of Allo-SCT for CEL is still limited. Further study is required to define the treatment strategy.
Clinical Trial,Phase II • Journal
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CSF3R (Colony Stimulating Factor 3 Receptor) • IL5 (Interleukin 5)
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CSF3R T618I • CSF3R mutation
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Jakafi (ruxolitinib) • Campath (alemtuzumab)
5ms
Philadelphia chromosome-negative myeloproliferative chronic neoplasms: is clonal hematopoiesis the main determinant of autoimmune and cardio-vascular manifestations? (PubMed, Front Med (Lausanne))
In summary, the presence of CHIP, with or without neoplasia, can be associated with autoimmune manifestations and thrombosis. In the presence of these manifestations, it is necessary to consider a "disease-modifying therapy" that may either reduce the clonal burden or inhibit the clonally activated JAK pathway.
Review • Journal
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DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)
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DNMT3A mutation • TET2 mutation • JAK2 V617F • JAK2 mutation
5ms
Rusfertide Improves Markers of Iron Deficiency in Patients with Polycythemia Vera (ASH 2023)
Treatment with rusfertide resulted in rapid, robust, and sustained reduction in HCT levels in PV patients with elevated HCT levels at baseline. Treatment resulted in normalization of iron parameters as noted by increases in ferritin, and normalization of serum iron and MCV in patients who were iron deficient at baseline. Improvements in iron deficiency following rusfertide are suggestive of clinical benefits and merit further investigation.
Clinical
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ERFE (Erythroferrone)
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rusfertide (PTG-300)
5ms
Acquired Von Willebrand Syndrome, Epidemiology, Laboratory Findings and Molecular Alterations on Classic Myeloproliferative Neoplasms in Mexican Population (ASH 2023)
Lastly, 96.7% of the patients were treated with hydroxyurea, which corrected cellular alterations and laboratory abnormalities found in AvWS... AvWS can be found in patients with platelet counts below 1,000 x103/µL, especially among those with PV with elevated Hb and Hct levels. This may deem it necessary to carry out diagnostic tests in patients with MPN and any degree of thrombocytosis. To our knowledge, this is the most comprehensive study among latin american patients that describes the coexistence of PMF and AvWS; even though the mechanism by which some PMF patients develop AvWS is not perfectly understood.
Clinical
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JAK2 (Janus kinase 2) • CALR (Calreticulin)
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JAK2 mutation
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hydroxyurea
5ms
Ruxolitinib in Treating Patients With Hypereosinophilic Syndrome or Primary Eosinophilic Disorders (clinicaltrials.gov)
P2, N=10, Recruiting, William Shomali | N=25 --> 10 | Trial completion date: Oct 2023 --> Nov 2025 | Trial primary completion date: Apr 2023 --> Nov 2025
Enrollment change • Trial completion date • Trial primary completion date
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JAK2 (Janus kinase 2) • ETV6 (ETS Variant Transcription Factor 6) • PCM1 (Pericentriolar Material 1)
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JAK2 mutation • JAK2 rearrangement
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Jakafi (ruxolitinib)
5ms
Patient-reported Outcomes and Quality of Life in Anemic and Symptomatic Patients With Myelofibrosis: Results From the MOMENTUM Study. (PubMed, Hemasphere)
Improvements favored momelotinib versus danazol for each MFSAF individual item, and greater improvements were observed for disease- and cancer-related fatigue and physical functioning at week 24, with significant results for multiple items/domains across the 3 assessments. These findings are consistent in demonstrating that momelotinib provides substantial symptom benefit.
Journal • HEOR • Patient reported outcomes
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JAK2 (Janus kinase 2) • JAK1 (Janus Kinase 1) • ACVR1 (Activin A Receptor Type 1)
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Ojjaara (momelotinib)
6ms
Case Report - JAK2 Exon 16 Mutation in AYA-cMPN (DGHO 2023)
Following a consultation with a dermatologist due to progressive hair loss in september of 2022, subsequent blood sampling led to the incidental finding of thrombocytosis whereupon the patient became a part of the regional register cMPN of Lüdenscheid. History taking revealed two cases of breast cancer, affecting both the already deceased maternal grandmother and great-aunt. The patient herself reported about two episodes of word finding difficulties in the beginning of 2022, which have not been clarified by imaging.
Clinical
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JAK2 (Janus kinase 2)
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JAK2 mutation
7ms
Renin-angiotensin inhibitors reduce thrombotic complications in Essential Thrombocythemia and Polycythemia Vera patients with arterial hypertension. (PubMed, Ann Hematol)
In particular, patients with ET and a high risk of thrombosis seem to benefit most from RASi treatment (HR = 0.27; 95%CI 0.07-1.01, p = 0.03). Hypertension in MPN patients represents a significant risk factor for TAEs and should be adequately treated.
Journal
7ms
Revisiting Circulating Extracellular Matrix Fragments as Disease Markers in Myelofibrosis and Related Neoplasms. (PubMed, Cancers (Basel))
Considering that MPNs are acquired clonal stem cell diseases developing in an inflammatory microenvironment in which the hematopoietic cell populations are progressively replaced by stromal proliferation-"a wound that never heals"-we herein aim to provide a comprehensive review of previous promising research in the field of circulating ECM fragments in the diagnosis, treatment and monitoring of MPNs. We address the rationales and highlight new perspectives for the use of circulating ECM protein fragments as biologically plausible, noninvasive disease markers in the management of MPNs.
Review • Journal
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JAK2 V617F
7ms
A Journey Through JAK Inhibitors for the Treatment of Myeloproliferative Diseases. (PubMed, Curr Hematol Malig Rep)
Several JAKi are available and used worldwide, and combination approaches are now being explored. In this chapter, we review the approved JAKi, highlighting its strengths, exploring potential guidelines in choosing which one to use and reasoning towards future perspectives, where the combinations of therapies seem to promise the best results.
Review • Journal
7ms
Optimization of cardiovascular risk factor management in patients with BCR::ABL1 negative chronic myeloproliferative neoplasms, current knowledge, and perspectives. (PubMed, Ann Hematol)
Moreover, the optimal target levels for different metabolic deflections in MPNs (i.e., low-density lipoprotein, serum uric acid, or glycated hemoglobin levels) have not been defined. In the current review, we separately discuss the most important aspects of every individual CV risk factor (arterial hypertension, hyperlipidemia, chronic kidney disease, smoking, diabetes mellitus, hyperuricemia, and obesity and cachexia) in MPNs, summarize recent advances in the field, and propose future directions and research areas which may be needed to appropriately manage CV risk factors in MPNs.
Review • Journal
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ABL1 (ABL proto-oncogene 1)
7ms
Associations of JAK2 Mutant Allele Burden With Occurrence of CKD (Chronic Kidney Disease) and Dynamics of Kidney Function Over Time in Patients With Chronic Myeloproliferative Neoplasms (SOHO 2023)
MPN patients with higher MAB seem to have a higher occurrence of concomitant CKD and demonstrate unfavorable dynamics of kidney function over time. Although causal relationship cannot be inferred due to limitations of the study design, our observations support the view that biology of MPN and CKD might be intertwined.
Clinical
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JAK2 (Janus kinase 2)
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JAK2 V617F • JAK2 mutation
7ms
Whole blood transcriptional profiling reveals highly deregulated atherosclerosis genes in Philadelphia-chromosome negative myeloproliferative neoplasms. (PubMed, Eur J Haematol)
We have for the first time shown massive deregulation of atherosclerosis genes in MPNs, likely reflecting the inflammatory state in MPNs in association with in vivo activation of leukocytes, platelets, and endothelial cells being deeply involved in the atherosclerotic process.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • PDGFA (Platelet Derived Growth Factor Subunit A) • MMP1 (Matrix metallopeptidase 1) • PTGS1 (Prostaglandin-Endoperoxide Synthase 1)
8ms
Acquired elliptocytosis in chronic myeloid neoplasms: An enigmatic relationship to acquired red cell membrane protein and genetic abnormalities. (PubMed, Blood Cells Mol Dis)
Moreover, in one case a specific qualitative abnormality of red cell protein band 4.1(4.1R) was reported; however, several subsequent cases could find no abnormality of a red cell membrane protein or found a different abnormality, usually quantitative. Thus, this striking red cell phenotypic feature, acquired elliptocytosis, seen in myelodysplastic syndrome and other chronic myeloproliferative diseases, closely simulating the red cell phenotype of hereditary elliptocytosis, has an unexplained genetic basis, presumably as the result of an acquired mutation(s) in some chronic myeloid neoplasms.
Review • Journal
8ms
Essential Thrombocythemia and Ischemic Stroke: A Case Series of Five JAK2-Positive Patients. (PubMed, Medicina (Kaunas))
The study highlights combined use of antiplatelet and cytoreductive therapy in preventing secondary stroke events in patients with ET and JAK2 mutations. The heterogeneity of stroke patterns in this population necessitates a comprehensive understanding of the underlying pathophysiological mechanisms and tailored therapeutic approaches.
Journal
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JAK2 (Janus kinase 2)
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JAK2 mutation
8ms
Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety. (PubMed, J Hematol Oncol)
There is a focus on the occurrence of common hematologic and nonhematologic adverse events, with guidance provided on the management of patients with anemia or thrombocytopenia, including dosing strategies based on findings from the REALISE and EXPAND trials. Finally, to ensure a greater understanding of the safety profile of ruxolitinib, practical considerations are discussed.
Review • Journal
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Jakafi (ruxolitinib)
8ms
Clinical Flow Cytometry Analysis in the Setting of Chronic Myeloid Neoplasms and Clonal Hematopoiesis. (PubMed, Clin Lab Med)
The utility of flow cytometry analysis in the evaluation of chronic myeloid neoplasms, such as myelodysplastic neoplasms and chronic myeloproliferative neoplasms, continues to be emphasized and explored. Recently flow cytometry analysis has been also proven to be able to distinguish persistent clonal hematopoiesis from measurable residual disease in patients with acute myeloid leukemia (AML), a finding with potential critical treatment impact in the management of patients with AML.
Review • Journal
9ms
Efficacy and safety of peginterferon-α2b for treatment of myeloproliterative neoplasms (PubMed, Nan Fang Yi Ke Da Xue Xue Bao)
For patients with chronic myelodysplasia, peginterferon-α2b treatment can achieve a high peripheral blood cell remission rate and maintain a long-term stable state with good effect in relieving symptoms such as splenomegaly. Peginterferon- α2b treatment caused only mild adverse reactions, which can be tolerated by most of the patients.
Journal
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JAK2 V617F
9ms
Myeloid sarcoma: more and less than a distinct entity. (PubMed, Ann Hematol)
Role and type of consolidation therapy are not univocally acknowledged, and systemic therapies, radiotherapy, or allogeneic hematopoietic stem cell transplantation (allo-HSCT) should be considered. In the present review, we discuss recent information on MS, focusing on diagnosis, molecular findings, and treatments also considering targetable mutations by recently approved AML drugs.
Review • Journal
9ms
The international consensus classification of eosinophilic disorders and systemic mastocytosis. (PubMed, Am J Hematol)
This review is to focus on the ICC updates related to these disease entities, illustrated through changes related to morphology, molecular genetics, clinical features, prognosis, and treatment. Two practical algorithms are provided in navigating through the diagnosis and classification systems of hypereosinophilia and SM.
Review • Journal
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FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • JAK2 (Janus kinase 2) • ETV6 (ETS Variant Transcription Factor 6) • PCM1 (Pericentriolar Material 1)
9ms
Clonal Hematopoiesis in Myeloproliferative Neoplasms Confers a Predisposition to both Thrombosis and Cancer. (PubMed, Curr Hematol Malig Rep)
In summary, clonal hematopoiesis in MPN and CHIP confer a predisposition to cardiovascular events and cancer through chronic and systemic inflammation. This acquisition could open new avenues for antithrombotic therapy both in MPNs and in general population by targeting both clonal hematopoiesis and inflammation.
Review • Journal
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DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CALR (Calreticulin)
9ms
Advanced cutaneous squamous cell carcinoma induced by long-term Hydroxyurea treatment – a case report (WCD 2023)
Immunotherapy with Cemiplimab was initiated. If the latter is impossible low-dose retinoid or immunotherapy is recommended. Multiple studies and long-term follow-ups are needed to establish the therapeutic strategy in such cases
Clinical • Metastases
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Libtayo (cemiplimab-rwlc) • hydroxyurea