News - JAK2 V617F - LARVOL VERI

23h

Determination of the Clonality Profile in Myeloproliferative Neoplasms and Association With the Thrombotic Complications (CLOJAK) (clinicaltrials.gov)

P=N/A, N=120, Recruiting, University Hospital, Bordeaux | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

23 hours ago

Trial completion date • Trial primary completion date

JAK2 V617F

JAK2 p.R564 germ line variants associated with hereditary thrombocythemia and hematologic neoplasms. (PubMed, Blood Adv)

Identification of germline predisposition is essential to understanding the pathogenesis of disease, impact on families, and opportunities for preventive care. Continued research is essential to further characterize the penetrance of these conditions, and how best to monitor, treat and optimize management for these families.

3 days ago

Journal

JAK2 (Janus kinase 2)

JAK2 V617F • JAK2 mutation

Donor selection for allogeneic hematopoietic cell transplant in a patient with JAK2 V617F primary myelofibrosis and SH2B3/LNK germline variant. (PubMed, Ann Hematol)

The consideration of such inherited traits is crucial for clinical management of patients, particularly with regards to indication for allogeneic hematopoietic cell transplant (allo-HCT) and donor selections. Herein, we describe the very instructive case of a 49-year-old woman diagnosed with JAK2 V617F-positive primary myelofibrosis (PMF) who was found to also carry a germline variant in the SH2B3 gene, detailing clinical management, donor selection process for allo-HCT purposes, and appropriate genetic counseling.

5 days ago

Journal

JAK2 (Janus kinase 2) • SH2B3 (SH2B Adaptor Protein 3)

JAK2 V617F

Novel approaches in myelofibrosis. (PubMed, Hemasphere)

Finally, current efforts of generating novel endpoints for clinical trials aim more at disease modification and overall survival than at improvements of splenomegaly or symptoms. Together, the new generations of clinical trials promise to offer substantial improvements in the management of MF patients and long-term disease control.

6 days ago

Review • Journal • IO biomarker

TP53 (Tumor protein P53) • S100A8 (S100 Calcium Binding Protein A8) • PIM1 (Pim-1 Proto-Oncogene) • CALR (Calreticulin)

JAK2 V617F

A comparative retrospective study of pre-fibrotic primary myelofibrosis versus overtly fibrotic stage in Qatar: clinicopathological, genetic landscape, risk stratification and survival data (2008-2021) - a single center experience. (PubMed, Hematology)

To the best of our knowledge our research represents the first and largest published dataset on PMF in MENA region to be published. Merged DIPSS plus scoring came to be a pragmatic tool for defining high-risk patients who significantly differ in mortality, progression, need for treatment and leukemic transformation.

7 days ago

Clinical • Retrospective data • Journal

JAK2 (Janus kinase 2)

JAK2 V617F • JAK2 mutation

Prevalence of JAK 2 v617 Mutations in Malignant and Non-Malignant Tumors in the Eastern Province of the Kingdom of Saudi Arabia. (PubMed, Clin Lab)

We believe these observations warrant a comprehensive search for activated tyrosine kinases in myeloproliferative disorders and hematological malignancies, as there are likely additional unidentified genetic events with biological and therapeutic significance. Additional in vitro and in vivo studies are needed to determine the cause of the specificity of JAK2 V617F for myeloid and lymphoid diseases.

7 days ago

Journal

JAK2 (Janus kinase 2)

JAK2 V617F • JAK2 mutation

JAK2-V617F mutation among blood donors: A meta-analysis. (PubMed, Saudi Med J)

The prevalence of the JAK2 mutation among blood donors is similar to the general population's but slightly higher among repeat donors with elevated hematocrit. Further research is necessary to establish definitive upper hemoglobin limits for donor deferral.PROSPERO No.: CRD42023456878.

8 days ago

Clinical • Retrospective data • Review • Journal

JAK2 (Janus kinase 2)

JAK2 V617F • JAK2 mutation

Polycythemia vera with acute coronary syndrome and bleeding as initial presentation: A case report and literature review. (PubMed, Radiol Case Rep)

This case highlights the importance of considering myeloproliferative disorders in patients with atypical thrombotic and hemorrhagic events. It emphasizes the need for early diagnosis and appropriate treatment to optimize patient outcomes.

9 days ago

Review • Journal

JAK2 (Janus kinase 2)

JAK2 V617F • JAK2 mutation

Thromboinflammation in ischemic cerebrovascular patients with the JAK2V617F mutation. (PubMed, Thromb Res)

In ischemic cerebrovascular patients, the JAK2V617F mutation is associated with elevated markers of endothelial dysfunction and chronic inflammation. This underscores the role of inflammation in thrombosis driven by the JAK2V617F mutation.

9 days ago

Journal

TNFA (Tumor Necrosis Factor-Alpha) • IL10 (Interleukin 10) • VCAM1 (Vascular Cell Adhesion Molecule 1)

JAK2 V617F

19d

Molecular Profile of BCR-ABL1 Negative Myeloproliferative Neoplasm in a Moroccan Population. (PubMed, Asian Pac J Cancer Prev)

In conclusion, our study provides valuable insights into the prevalence and characteristics of JAK2, CALR, and MPL mutations in BCR-ABL1 negative MPNs in the Moroccan population, highlighting the importance of genetic characterization to optimize the clinical management of these diseases.

19 days ago

Journal

ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • JAK2 (Janus kinase 2) • CALR (Calreticulin) • STAT5A (Signal Transducer And Activator Of Transcription 5A) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)

JAK2 V617F • JAK2 mutation • CALR mutation • STAT5A mutation

29d

LNK/SH2B3 Loss Exacerbates the Development of Myeloproliferative Neoplasms in CBL-deficient Mice. (PubMed, Stem Cell Rev Rep)

Further analysis confirmed a positive role of LNK in regulating proteasome activity, independent of its well-established function in signaling transduction. Thus, our work reveals a novel function of LNK in coordinating with the E3 ligase CBL to regulate myeloid malignancies.

29 days ago

Preclinical • Journal

KIT (KIT proto-oncogene, receptor tyrosine kinase) • SH2B3 (SH2B Adaptor Protein 3)

CBL mutation • JAK2 V617F • KIT expression

Target-Capture Next-Generation Sequencing (NGS) for Use in Molecular-Based Research of Myeloid Measurable Residual Disease (MRD) (AMP 2024)

Target-capture NGS provides the opportunity to evaluate many genes in a single assay. Suitability for MRD requires highly uniform and sensitive target enrichment. Our study demonstrated reliable and accurate detection of variants down to 0.05% VAF, providing researchers with the capability to use capture-based NGS for myeloid MRD monitoring.

1 month ago

Next-generation sequencing

FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • JAK2 (Janus kinase 2)

FLT3-ITD mutation • NPM1 mutation • FLT3 D835Y • FLT3 D835 • IDH2 R172K • KIT D816V • IDH1 R132C • JAK2 V617F • IDH1 R132 • IDH2 R172

SureSeq™ Myeloid MRD Panel

DNA and RNA NGS for Myeloid Neoplasms Using Oncomine Myeloid Assay GX v2 on GeneXus: An Assessment of Clinical Utility (AMP 2024)

This DNA- and RNA-based 80-gene panel has proven to be a powerful tool for genomic profiling of myeloid neoplasms. The results were provided to hematopathologists/oncologists in timely fashion with the critical information for diagnosis confirmation, and disease classification, as well as assessment of patient response to treatment.

1 month ago

Clinical • Next-generation sequencing

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • DDX41 (DEAD-Box Helicase 41) • CALR (Calreticulin) • ZRSR2 (Zinc Finger CCCH-Type, RNA Binding Motif And Serine/Arginine Rich 2)

FLT3-ITD mutation • NPM1 mutation • U2AF1 mutation • CEBPA mutation • JAK2 V617F

Oncomine Myeloid Assay GX

Performance of Pillar oncoReveal Essential MPN Panel: Experiences of Two Clinical Diagnostic Laboratories (AMP 2024)

This intra-laboratory study demonstrates that the oncoReveal Essential MPN Panel performed very well against comparator methods. The performance characteristics, workflow benefits, and TAT saving are suitable for clinical testing of MPN patient population to allow accurate clinical assessment.

1 month ago

Clinical

JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 V617F

ONCO/Reveal™ Essential MPN Panel

DNMT3A, TET2, and ASXL1 (DTA) Mutations Are Associated with Thrombosis and Bleeding in Patients with Myeloproliferative Neoplasms (ASH 2024)

Conclusions : DTA mutations detected with a clinically used NGS panel in patients with MPN are associated with increased risk of bleeding complications, as well as increased thrombotic risk in a subgroup of patients. These findings support the incorporation of molecular panel analyses in thrombosis and bleeding risk assessment in MPN, and merit further investigation.

1 month ago

Clinical

DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CALR (Calreticulin)

ASXL1 mutation • TET2 mutation • JAK2 V617F • JAK2 mutation

Archer® VariantPlex® Myeloid panel

2ms

JAK 2-Positive Diseases and Spontaneous Coronary Artery Dissection: Case Series. (PubMed, Case Rep Oncol)

MPNs with JAK2 mutations are associated with SCAD in addition to usual atherosclerosis. This association needs further research.

2 months ago

Journal

JAK2 (Janus kinase 2)

JAK2 V617F • JAK2 mutation

2ms

Features and allele frequency of JAK2 Exon 12-mutated polycythemia vera in comparison with JAK2V617F-mutated disease. (PubMed, Arch Med Res)

Taiwanese patients with PV showed differences in blood count, risk group, and bleeding events between exon 12 and JAK2V617F patients. Higher mutant allele burden had a negative impact on overall survival for both mutation types.

2 months ago

Journal

JAK2 (Janus kinase 2)

JAK2 V617F • JAK2 mutation

2ms

New approaches to standard of care in early-phase myeloproliferative neoplasms: can interferon-α alter the natural history of the disease? (PubMed, Haematologica)

Finally, we present the interferon alpha (IFNα) therapy as a potential early disease-modifying drug after reporting its good hematological and molecular efficacies in ET, PV and early MF in clinical trials as well as its mechanism of action in pre-clinical studies. As a result, we may expect that, in the future, MPN patients will be diagnosed very early during the course of disease and that new selective therapies under development, such as IFNα, JAK2V617F inhibitors and CALRmut monoclonal antibodies, would be able to intercept the mutated clones.

2 months ago

Journal

CALR (Calreticulin) • IFNA1 (Interferon Alpha 1)

JAK2 V617F

2ms

JAK2V617F-dependent down regulation of SHP-1 expression participates in the selection of myeloproliferative neoplasm cells in the presence of TGF-β. (PubMed, J Cell Mol Med)

In conclusion, we show a JAK2-dependent down regulation of SHP-1 in MPN patients' cells which is related to their resistance to the antiproliferative effect of TGF-β. This may participate in the clonal selection of cancer cells in MPNs.

2 months ago

Journal

JAK2 (Janus kinase 2) • CD34 (CD34 molecule) • TGFB1 (Transforming Growth Factor Beta 1)

JAK2 V617F • CD34 positive

2ms

Essential Thrombocythemia Possible Cause of Ischemic Cerebrovascular Disease: A Case Report. (PubMed, Cureus)

Antiplatelet therapy was started with acetylsalicylic acid 100 mg and clopidogrel 75 mg once a day. With the recommendation of hematology, cytoreductive treatment, hydroxyurea 1000 mg twice a day, was started. The patient's complaints were resolved at the end of the second day, and the patient with minimal ataxia was discharged with recommendations. Patients with ET should be aware of ischemic cerebrovascular disease and consider antiplatelet and cytoreductive treatment options.

2 months ago

Journal

JAK2 (Janus kinase 2)

JAK2 V617F • JAK2 mutation

hydroxyurea

2ms

Absence of canonical mutations in pediatric essential thrombocytosis: a case series. (PubMed, Blood Res)

No patient experienced hemorrhagic or thrombotic complications. Our case series emphasizes that the genetic features of pediatric ET may differ significantly from those of adult ET, and that treatment cessation is a possibility for some patients.

2 months ago

Journal

JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 V617F

2ms

JAK Inhibitors for Myelofibrosis: Strengths and Limitations. (PubMed, Curr Hematol Malig Rep)

Recently, there has been increased efforts to optimize treatment with the development of highly selective JAK inhibitors, as well as use of combination agents to counter disease resistance through targeting aberrant signaling pathways. Treatment of MF patients with JAKi therapy can be challenging but the development of more potent and selective JAK inhibitors, as well as combination therapies, represent exciting treatment advances in this field.

2 months ago

Review • Journal

JAK2 (Janus kinase 2)

JAK2 V617F • JAK2 mutation

2ms

Cerebral venous sinus thrombosis associated with JAK2 V617F mutation-related pre-primary myelofibrosis: a case report and literature review. (PubMed, BMC Neurol)

This case highlights the importance of recognizing dynamic changes in routine blood tests that may link CVST to underlying hematological disorders. The JAK2 mutation is not only associated with MPNs but also increases the risk of thrombosis, including CVST. Further investigation is warranted to better understand the mechanisms by which JAK2 mutations contribute to thrombosis and to explore the potential benefits of JAK2 inhibitors in reducing this risk.

2 months ago

Review • Journal

JAK2 (Janus kinase 2)

JAK2 V617F • JAK2 mutation

aspirin

2ms

Effects of Ruxolitinib on Immune Checkpoint Molecule Expression in JAK2 V617F-Positive Cells. (PubMed, Clin Lab)

Ruxolitinib reduces the expression of p-JAK2, PD-1, and PD-L1 in JAK2 V617F-positive cells by specifically inhibiting the JAK2 signaling pathway, thereby suppressing the progression of MPNs.

2 months ago

Journal • PD(L)-1 Biomarker • IO biomarker

JAK2 (Janus kinase 2) • PD-1 (Programmed cell death 1)

PD-L1 expression • PD-1 expression • JAK2 V617F • JAK2 mutation

Jakafi (ruxolitinib)

2ms

Neutrophil/lymphocyte ratio identifies low-risk polycythaemia vera patients for early Ropeginterferon alfa-2b therapy. (PubMed, Br J Haematol)

Interestingly, the reduction in JAK2 VAF from baseline was linearly associated with the reduction in NLR. Patients who failed Phl-O at 12 months had characteristics that distinguished them from responders, including very high NLR and resistance to cross-over to 100 μg Ropeg every 2 weeks suggesting higher escalated doses of Ropeg. In conclusion, the study provides evidence that NLR can serve as a valuable biomarker to assess and guide treatment with Ropeg in the early stage of low-risk PV patients.

2 months ago

Journal

JAK2 (Janus kinase 2)

High NLR • JAK2 V617F

Besremi (ropeginterferon alfa-2b-njft)

2ms

Childhood and adolescent essential thrombocythemia and prefibrotic primary myelofibrosis: insights into diagnosis, outcomes, and treatment from a large Chinese cohort. (PubMed, Leukemia)

Compared to CAA-ET, CAA-preMF demonstrated poorer progression-free survival (P < 0.001) and faster disease progression (P = 0.019). This study provides a critical foundation for refining diagnostic, prognostic, and therapeutic approaches for CAA-ET and CAA-preMF.

2 months ago

Journal

JAK2 (Janus kinase 2)

JAK2 V617F

2ms

Variance quantitative trait loci reveal gene-gene interactions which alter blood traits. (PubMed, medRxiv)

This approach identified (1) a known interaction for hemoglobin between two pathogenic variants in HFE which cause hereditary hemochromatosis and alters risk of cirrhosis and (2) a novel interaction between the JAK2 46/1 haplotype and a variant on chromosome 14 which modifies platelet count, JAK2 V617F clonal hematopoiesis, and risk of polycythemia vera. This work identifies novel disease-relevant GxG interactions and demonstrates the utility of vQTL-based approaches in identifying GxG interactions relevant to human health at scale.

2 months ago

Journal

JAK2 (Janus kinase 2) • HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ Beta 1) • HLA-DQA1 (Major Histocompatibility Complex, Class II, DQ Alpha 1)

JAK2 V617F

2ms

Synergistic effect of concurrent high molecular risk mutations and lower JAK2 mutant variant allele frequencies on prognosis in patients with myelofibrosis-insights from a multicenter study. (PubMed, Leukemia)

Importantly, the integration of HMR/JAK2V617F VAF (≤50%) status significantly enhanced existing prognostic models, as evidenced by higher c-indexes and time-dependent ROC analyses. Single-cell studies with sequential follow-ups are warranted to decipher the clonal evolution of MF and how it relates to JAK2V617F VAF dynamics.

2 months ago

Clinical • Journal

JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • SRSF2 (Serine and arginine rich splicing factor 2)

EZH2 mutation • SRSF2 mutation • JAK2 V617F • JAK2 mutation

3ms

Relation of JAK2 V617F allele burden and coronary calcium score in patients with essential thrombocythemia. (PubMed, Radiol Oncol)

The average JAK2 allele burden decreased in our patients with high-risk ET during the four-year period. However, in the small subgroup whose JAK2 mutation burden increased the Agatston coronary calcium score increased as well. This finding, which should be interpreted with caution and validated in a larger group, is in line with emerging evidence that JAK2 mutation accelerates atherosclerosis and can be regarded as a non-classical risk factor for cardiovascular disease.

3 months ago

Journal • Tumor mutational burden

TMB (Tumor Mutational Burden) • JAK2 (Janus kinase 2)

JAK2 V617F • JAK2 mutation

3ms

Long-term safety and efficacy of ropeginterferon alfa-2b in Japanese patients with polycythemia vera. (PubMed, Int J Hematol)

All patients experienced adverse events; 25/27 (92.6%) experienced adverse drug reactions (ADRs), but no serious ADRs or deaths occurred. This interim analysis demonstrated the safety and efficacy of ropegIFN over 36 months in Japanese patients with PV.

3 months ago

Journal

JAK2 (Janus kinase 2)

JAK2 V617F

Besremi (ropeginterferon alfa-2b-njft)

3ms

Differential modulation of mutant CALR and JAK2 V617F-driven oncogenesis by HLA genotype in myeloproliferative neoplasms. (PubMed, Front Immunol)

In conclusion, the HLA-I genotype differentially restricts JAK2 V617F and CALRmut-driven oncogenesis potentially explaining the mutual exclusivity of the two mutations and differences in their presentation latency. These findings have practical implications for the development of neoantigen-based vaccines in MPNs.

3 months ago

Journal

JAK2 (Janus kinase 2) • CALR (Calreticulin) • TAP1 (Transporter 1)

JAK2 V617F • CALR mutation • TAP1 expression

3ms

Janus kinase inhibitor monotherapy and combination therapies for myelofibrosis: what's the current standard of care? (PubMed, Expert Rev Hematol)

In order to potentially increase clinical benefit for patients with MF, several novel agents are being partnered with ruxolitinib (RUX) with the ongoing hypothesis to augment greater measures of MF disease modification. The novel agents are either 'added-on' to RUX or as a combo in JAKi naïve patients. Also, the mutant-targeting era of therapies is now beginning with novel CALR-mutated, novel JAK2 V617F mutation-specific and type II JAK2i in the initial stages of drug development, representing a new approach to treatment.

3 months ago

Review • Journal • Combination therapy

JAK2 (Janus kinase 2) • CALR (Calreticulin)

JAK2 V617F • JAK2 mutation • CALR mutation

Jakafi (ruxolitinib)

3ms

Reduced platelet activation in triple-negative essential thrombocythemia compared with JAK2V617F-mutated essential thrombocythemia. (PubMed, Clin Cancer Res)

In comparison to JAK2V617F-mutated ET, TN-ET is associated with lower platelet ROS levels, which leads to reduced platelet activation and consequently a lower risk of thrombosis.

3 months ago

Clinical • Journal

SELP (Selectin P)

JAK2 V617F

3ms

Exogenous Janus Kinase 617 Codon Influences Small Noncoding RNAs and Gene Expression in Ba/F3 Cells. (PubMed, J Physiol Investig)

The induction route is functionally conserved, according to exogenously produced miRNA and gene expression. These results may clarify how the JAK2V617F induces transformation.

3 months ago

Journal

JAK2 (Janus kinase 2)

JAK2 V617F

3ms

Elotuzumab for the Treatment of JAK2-Mutated Myelofibrosis (clinicaltrials.gov)

P2, N=15, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

3 months ago

Trial completion date • Trial primary completion date • IO biomarker

JAK2 (Janus kinase 2) • IL1R1 (Interleukin 1 receptor, type I) • SLAMF7 (SLAM Family Member 7)

JAK2 V617F

Empliciti (elotuzumab)

3ms

P1101 in Treating Patients with Myelofibrosis (clinicaltrials.gov)

P2, N=11, Completed, Mayo Clinic | Active, not recruiting --> Completed | Trial completion date: Aug 2024 --> Nov 2023 | Trial primary completion date: Aug 2024 --> Nov 2023

3 months ago

Trial completion • Trial completion date • Trial primary completion date

JAK2 V617F

Besremi (ropeginterferon alfa-2b-njft)

3ms

New advances in the role of JAK2 V617F mutation in myeloproliferative neoplasms. (PubMed, Cancer)

This requires an in-depth understanding of the mechanism of action of the JAK2 V617F mutation. In this review, the authors explored the role of the JAK2 V617F mutation in MPN from multiple aspects, including the mechanisms of non-JAK/STAT pathways, the regulation of cellular methylation, the induction of cellular DNA damage accumulation, and effects on the cardiovascular system, with the objective of providing valuable insights into multidrug combination therapy for MPN.

3 months ago

Review • Journal

JAK2 (Janus kinase 2)

JAK2 V617F • JAK2 mutation

3ms

Challenges in Diagnosing Polycythemia Vera in Primary Care: A 55-Year-Old Malaysian Woman with Atypical Presentation. (PubMed, Am J Case Rep)

Treatment with phlebotomy, hydroxyurea, and aspirin resulted in significant improvements in ocular symptoms and hematological parameters within 60 days. CONCLUSIONS This case underscores the critical role of primary care in the early detection of polycythemia vera. Timely identification and appropriate referral from primary care settings are essential to avoid diagnostic delays and ensure effective management, improving patient outcomes and preventing complications.

3 months ago

Journal

JAK2 (Janus kinase 2)

JAK2 V617F • JAK2 mutation

hydroxyurea • aspirin

3ms

The survivin/XIAP suppressant YM155 impairs clonal growth and induces apoptosis in JAK2V617F cells. (PubMed, Hematol Transfus Cell Ther)

Protein expression analysis corroborates the observed cellular phenotype and exploratory gene expression findings. In summary, our results indicate that survivin/BIRC5 and XIAP are differently expressed in myeloproliferative neoplasms and YM155 has multiple antineoplastic effects on JAK2V617F cells suggesting that inhibitor of apoptosis proteins may be a target for pharmacological interventions in the treatment of these diseases.

3 months ago

Journal

XIAP (X-Linked Inhibitor Of Apoptosis)

JAK2 V617F • BIRC5 expression

sepantronium bromide (PC-002)

3ms

Impaired fibrinolysis in JAK2V617F-related myeloproliferative neoplasms. (PubMed, J Thromb Haemost)

Our results suggest that impaired tPA-mediated fibrinolysis represents an important pro-thrombotic mechanism in MPN patients that requires confirmation on larger studies.

3 months ago

Journal

CALR (Calreticulin)

JAK2 V617F • CALR mutation

3ms

Immune-dysregulation harnessing in myeloid neoplasms. (PubMed, Cancer Med)

In this review, we discuss the role of altered bone marrow microenvironments in the induction of immune dysregulations that accompany myeloid malignancies. We also consider both current and novel therapeutic strategies to restore normal immune system function in the context of myeloid malignancies.

3 months ago

Review • Journal

TNFA (Tumor Necrosis Factor-Alpha)

JAK2 V617F

3ms

Involvement of CREB3L1 in erythropoiesis induced by JAK2 exon 12 mutation. (PubMed, Exp Hematol)

shRNA knockdown of CREB3L1 expression in HSPCs blocked erythroblast formation in vitro. These results suggest that CREB3L1 is required for erythropoiesis in the presence of JAK2 exon 12 mutation or high level of EPO, possibly by antagonizing cellular stress.

3 months ago

Journal

JAK2 (Janus kinase 2) • CREB3L1 (CAMP Responsive Element Binding Protein 3 Like 1)

JAK2 V617F • JAK2 mutation • CREB3L1 expression