Essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) are Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) characterized by increased myeloid proliferation. The gain of function induced by the Janus kinase 2 mutation, JAK2 V617F , has been reported in most PV and in more than half of ET and PMF cases. 1 However, the presence of different dis...

E ssential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) belong to the group of Philadelphia chromosome-negative myeloproliferative neoplasias (Ph-MPN). MPNs are clonal bone marrow stem cell disorders involving a multipotent hematopoietic stem cell, characterized by proliferation of one or more lineages of the myeloid, erythroid and megakaryocytic cell lines. This...

Essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) are Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) characterized by increased myeloid proliferation. The gain of function induced by the Janus kinase 2 mutation, JAK2 V617F , has been reported in most PV and in more than half of ET and PMF cases. 1 However, the presence of different dis...

Janus kinase 2 (JAK2) initiates signaling from several cytokine receptors and is required for biological responses such as erythropoiesis. JAK2 activity is controlled by regulatory proteins such as Suppressor of Cytokine Signaling (SOCS) proteins and protein tyrosine phosphatases. JAK2 activity is also intrinsically controlled by regulatory domains, where the pseudokinase (JAK homology 2, JH2) ...

The discovery of the JAK2V617F mutation triggered an unexpected flowering of basic and clinical studies in the field of myeloproliferative neoplasms (MPNs), resulting after just a few years in an exceptional amount of new information. One important consequence of those new findings was the modification of the World Health Organization classification and diagnostic algorithms for these diseases,...

We studied the relationship between granulocyte JAK2 (V617F) mutation status, circulating CD34(+) cells, and granulocyte activation in myeloproliferative disorders. Quantitative allele-specific polymerase chain reaction (PCR) showed significant differences between various disorders with respect to either the proportion of positive patients (53%-100%) or that of mutant alleles, which overall ran...

Janus kinases are essential for signal transduction by a variety of cytokine receptors and when inappropriately activated can cause hematopoietic disorders and oncogenesis. Consequently, it can be predicted that the interaction of the kinases with receptors and the events required for activation are highly controlled. In a screen to identify phosphorylation events regulating Jak2 activity in Ep...

Our knowledge of the genetic basis of these disorders began in 2005, when a unique base substitution in JAK2, the gene encoding Janus kinase 2,was found inpatientswith polycythemia vera, essential thrombocythemia, and primary myelofibrosis. The background of our investigations was the previous finding that copy-neutral loss of heterozygosity of chromosome 9p (9pLOH) is the most common chromosom...

BACKGROUND This study evaluated potential correlations between the allele burden of the Janus kinase 2 (JAK2) V617F mutation and clinicohematologic characteristics in patients with myeloproliferative neoplasms (MPN). METHODS Clinical and hematologic features were reviewed for 103 MPN patients, including patients with polycythemia vera (PV, 22 patients), essential thrombocythemia (ET, 64 patie...

JAK2 V617F and MPL W515L/K mutations have been reported in approximately 50% and 5% of the patients with essential thrombocythemia (ET), respectively. We investigated the frequency of MPL W515L/K mutations in a series of consecutive patients with ET and post-essential thrombocythemia myelofibrosis (post-ET MF). The study subjects were 63 patients diagnosed either with ET (N=59) or post-ET MF (N...