Chronic myeloproliferative neoplasms (MPN) are stem cell disorders driven by mutations in <i>JAK2, CALR</i>, or <i>MPL</i> genes and characterized by myeloid proliferation and increased blood cell counts.
Cases with t(9p24;v)/JAK2 are extremely rare; while such cases with a MPN presentation may resemble t(8;9)(p22;p24.1)/PCM1-JAK2, B-ALL cases presenting de novo B-ALL might belong to Ph-like B-ALL.
The hallmark of <i>BCR-ABL1</i>-negative myeloproliferative neoplasms (MPNs) is the presence of a driver mutation in <i>JAK2, CALR</i>, or <i>MPL</i> gene.
We show that metabolic alterations in hematopoietic cells are fundamental to the pathogenesis of mutant JAK2-driven myeloproliferative neoplasms (MPNs).
Age-related clonal hematopoiesis (ARCH/CHIP) is a frequent finding in the elderly and combinations with MPN driver mutations (JAK2, MPL, and CALR) have been described.
Developing Janus kinase 2 (JAK2) inhibitors has become a significant focus for small-molecule drug discovery programs in recent years because the inhibition of JAK2 may be an effective approach for the treatment of myeloproliferative neoplasm.
We have yet to understand why JAK2-positive myeloproliferative neoplasms (MPN) patients manifest different phenotypes despite harboring JAK2 mutations and what drives secondary transformations.
The majority (94%) of patients were positive for the JAK2V617F mutation, whilst in 29% recurrent ICVEs (range two to three) were noted prior to MPN diagnosis.
Analysis of 30 BCR/ABL1-negative, nonpolycythemia vera MPN identified 15 (50%) with JAK2V617F, 2 with MPL mutations (7%), and 8 with CALR mutations (27%).
We address recent updates in the genetics and epigenetics of MPN, the mechanisms of transformation by mutant calreticulin, advances in the biology and therapy of systemic mastocytosis, clinical updates on JAK2 inhibitors and other therapeutic approaches for patients with MPNs, cardiovascular toxicity related to tyrosine kinase inhibitors and the concept of treatment-free remission for patients with CML.
Peripheral blood or bone marrow samples were obtained from 56 patients newly diagnosed with MPN or previously diagnosed with MPN but not yet indicated for JAK2 inhibitor treatment between 2012 and 2016.
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR, or MPL mutations; additional disease features include bone marrow stromal reaction including reticulin fibrosis, abnormal cytokine expression, anemia, hepatosplenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival.
Key genetic aberrations include the BCR-ABL1 gene rearrangement in Philadelphia chromosome-positive chronic myelogenous leukemia (CML) and JAK2/MPL/CALR aberrations in Philadelphia chromosome-negative MPNs.