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| http://dx.doi.org/10.3109/10428194.2015.1115031 | DOI Listing |
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Successful treatment of myeloid blast phase chronic myelogenous leukemia with the JAK2 V617 F mutation by combination therapy with asciminib and ropeginterferon alfa-2b in an elderly patient.
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The co-occurrence of JAK2 V617F mutations and the BCR::ABL1 translocation in the same patient is rare, and the current standard treatment for aggressive myeloid blast phase chronic myeloid leukemia (CML-myeloid BP) with JAK2 V617F mutations remains inadequate, particularly in transplant-ineligible patients. Asciminib, a first-in-class allosteric inhibitor of BCR::ABL1 kinase that specifically targets the ABL1 myristoyl pocket, has emerged as a novel alternative to standard tyrosine kinase inhibitor (TKI) therapy. Ropeginterferon alfa-2b (ropegIFNα2b) is a novel site-selective, monopegylated recombinant human IFN with long-term safety and efficacy in patients with polycythemia vera (PV).
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Introduction: Copy number alterations of chromosome 9p, or parts thereof, impair immune response and confer immune-checkpoint therapy (ICT) resistance by direct elimination of immune-regulatory genes on this arm, notably interferon (IFN)-γ (at 9p24.1) and type I IFN (IFN-I) cluster (9p21.3) genes.
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The Janus kinase 2 (JAK2) V617F mutation activates the transcription pathway and has been well characterized as a driver of myeloproliferative neoplasms (MPNs). Recently, there has been a heightened interest in understanding germ line predisposition to hematologic malignancies such as MPN, including several reports of familial MPN. Here, we retrospectively analyzed medical records and data from genetic testing to describe 12 patients with germ line variants at amino acid position 564 of JAK2.
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Article Synopsis
- High-molecular risk (HMR) mutations, such as ASXL1 and IDH, are linked to poorer outcomes in myelofibrosis (MF) patients, particularly when combined with lower levels of the JAK2V617F variant allele frequency (VAF).
- Analysis of 124 MF patients showed that HMR mutations significantly impacted prognosis for those with lower JAK2V617F VAF, while this effect was not observed in patients with higher VAF levels.
- The study's findings indicate that having both HMR mutations and a lower JAK2V617F VAF (≤50%) serves as a strong independent risk factor for survival, improving existing prognostic models and prompting the need for further