DOI: 10.5581/1516-8484.20130074 The identification of the association of a JAK2 gene mutation with chronic myeloproliferative neoplasms (cMPN) negative for BCR-ABL(1,2) has allowed significant advances in the understanding of this group of hematologic diseases. The JAK2 gene, located on chromosome 9p24, encodes the JAK2 protein which is a cytoplasmic tyrosine kinase that plays an important role...

Abstract Objective JAK2 is a non-receptor tyrosine kinase that plays a major role in myeloid disorders. JAK2V617F mutation is characterized by a G to T transverse at nucleotide 1849 in exon 12 of the JAK2 gene, located on the chromosome 9p, leading to a substitution of valine to phenylalanine at amino acid position 617 in the JAK2 protein. Methods In this study we evaluated RNA from 89 pati...

BACKGROUND Dysregulated signaling of the JAK/STAT pathway is a common feature of chronic myeloproliferative neoplasms (MPN), usually associated with JAK2V617F mutation. Recent clinical trials with JAK2 inhibitors showed significant improvements in splenomegaly and constitutional symptoms in patients with myelofibrosis but meaningful molecular responses were not documented. Accordingly, there re...

Myeloproliferative neoplasms (MPNs) are clinically characterized by the chronic overproduction of differentiated peripheral blood cells and the gradual expansion of malignant intramedullary/extramedullary hematopoiesis. In MPNs mutations in JAK2 MPL or CALR are detected mutually exclusive in more than 90% of cases [1,2]. Mutations in them lead to the abnormal activation of JAK/STAT signaling an...

BACKGROUND Pegylated-interferon alpha (PegINFα) treatment of patients with polycythemia vera (PV) and essential thrombocythemia (ET) has resulted in long-term clinical response, decreased JAK2V617F allelic burden and restoration of polyclonal hematopoiesis. The mechanisms of the beneficial effects of PegINFα are not clear, but available evidence suggests direct suppression of JAK2-mutated clone...

Essential thrombocythemia (ET) is a clonal myeloproliferative disorder characterized by overproduction of megakaryocytes (MKCs) and platelets. The recent discovery of the JAK2 mutation has shed a new light on the development of ET but its pathogenesis still remains unknown. One of the possible mechanisms can be deregulation of apoptosis, resulting in accumulation of bone marrow MKCs. In this st...

JAK2V617F, an activation mutant form of tyrosine kinase JAK2, is found in the majority of patients with myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis. Overwhelming studies have demonstrated the pathogenicity of JAK2V617F. However, some still doubt that JAK2V617F is a primary molecular defect in causing the malignan...

The discovery of mutations in calreticulin (CALR) in patients with primary myelofibrosis (PMF) prompted a reappraisal of the clinical correlates and prognostic impact of the so-called driver mutations that include JAK2V617F, MPLW515L/K/A and CALR in ~ 60%, 5–10% and 20–25% of patients, respectively. As compared with their JAK2V617F counterpart, PMF patients harboring CALR mutations showed young...