In 2005, multiple groups identified a high frequency of the V617F (G→T) mutation in the tyrosine kinase gene JAK2 as the most common molecular abnormality in chronic myeloproliferative disorders. Before 2005, there had been no recurring cytogenetic abnormality described at a high incidence in these disorders. The initial descriptions could well be classified as discovery papers because each gro...

We investigated a large number of acute myeloid leukemia (AML) samples (n=959) for the presence of the JAK2 V617F mutation. We found a low incidence of the mutation in these AML samples (1%). JAK2 V617F mutations clustered in AML samples with an aberrant karyotype (p<0.05). The incidence of JAK2 V617F in patients with a core binding factor (CBF) leukemia was 3.6% (p<0.01). Moreover, JAK2 V617F ...

A JAK2(V617F) mutation is found in approximately 55% of patients with essential thrombocythemia (ET), and represents a key World Health Organization diagnostic criterion. This hypothesis-generating study (NCT01352585) explored the impact of JAK2(V617F) mutation status on treatment response to anagrelide in patients with ET who were intolerant/refractory to their current cytoreductive therapy. T...

JAK2, an acquired mutation of JAK2, is present in a majority of patients with polycythemia vera and to a lesser extent among patients with the other myeloproliferative disorders. We analyzed the effect of JAK2 on the expression of polycythemia rubra vera 1(PRV-1), using an in vitro model. Compared to wild-type JAK2, the presence of JAK2 increased both PRV-1 protein and mRNA levels in murine mye...

Jak2 tyrosine kinase is essential for animal development and hyperkinetic Jak2 function has been linked to a host of human diseases. Control of this pathway using Jak2-specific inhibitors would therefore potentially serve as a useful research tool and/or therapeutic agent. Here, we used a high-throughput program called DOCK to predict the ability of 20,000 small molecules to interact with a str...

Refractory anemia with ring sideroblasts (RARS) is a myelodysplastic syndrome characterized by an anemia in which at least 15% of bone marrow erythroblasts are ringed sideroblasts. A percentage of RARS patients (10%-20%) eventually present high platelet counts ( 500 109/L), which may be due to reactive thrombocytosis or secondary myeloproliferative disorder (MPD).1-3 The recently discovered V61...

The purpose of this study was to develop a real time polymerase chain reaction (PCR) assay for the detection of the JAK2 V617F mutation that could be used in diagnostic laboratories. Sanger sequencing and a newly developed locked nucleic-acid, real-time PCR assay were used to detect the JAK2 V617F mutation. There was 100% agreement between the sequencing and PCR analysis. Both assays were able ...

We searched for JAK2 exon 12 mutations in patients with JAK2 (V617F)-negative myeloproliferative disorders. Seventeen patients with polycythemia vera (PV), including 15 sporadic cases and 2 familial cases, carried deletions or duplications of exon 12 in circulating granulocytes but not in T lymphocytes. Two of the 8 mutations detected were novel, and the most frequent ones were N542-E543del and...

JAK2 is a tyrosine kinase that plays an important role in the signaling pathways of many hematopoietic growth factor receptors. A single acquired point mutation – V617F – in JAK2 occurs in the great majority of patients with polycythemia vera (PV) and approximately half of the patients with idiopathic myelofibrosis (IMF) or essential thrombocythemia (ET). In contrast, the JAK2-V617F mutation is...

The JAK2 V617F mutation present in over 95% of Polycythemia Vera patients and in 50% of Essential Thrombocythemia and Primary Myelofibrosis patients renders the kinase constitutively active. In the absence of a three-dimensional structure for the full-length protein, the mechanism of activation of JAK2 V617F has remained elusive. In this study, we used functional mutagenesis to investigate the ...