The recent discovery of a recurrent activating Janus tyrosine kinase (JAK2) mutation (JAK2VG17F) in all 3 classic MPDs offers another opportunity for refining current diagnoses and disease classifications.
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%).
In addition, it provides evidence that despite the fact that angiogenesis is generally independent of the JAK2-V617F status in MPN, new vessel formation might be linked to Jak2 effects in some cases with high JAK2-V617F mutant allele burden.
The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) share similar molecular characteristics in that they frequently harbor hotspot mutations in JAK2, CALR or MPL, leading to activated JAK/STAT signaling.
Considerable attention has focused on the gain-of-function mutations in the Janus kinase-2 (JAK2) tyrosine kinase that are detectable in most patients with a myeloproliferative neoplasm.
In mice, tamoxifen treatment blocked development of JAK2(V617F)-induced myeloproliferative neoplasm in vivo, induced apoptosis of human JAK2(V617F+) HSPCs in a xenograft model, and sensitized MLL-AF9(+) leukemias to chemotherapy.
Involvement of JAK2 in erythroid cell proliferation has been highlighted by the role of JAK2V617F mutation in polycythemia vera (PV), a myeloproliferative disorder characterized by erythroid lineage overproduction.
Overall, these data indicate that TaqMan technology significantly improved sensitivity in detecting the JAK2 mutation in cMPD patients and may be worth of further evaluations as a clinically useful tool for detection of small amounts of mutated clones.
A variety of acquired mutations targeting JAK2 exon 12 are present in those patients with the myeloproliferative neoplasm, polycythemia vera, that lack the more common JAK2V617F mutation.
We conclude that multiple molecular abnormalities are involved in the pathogenesis of the MPDs and that aberrant Mpl expression may be a common denominator of aberrant signaling in both the JAK2V617F-positive and JAK2V617F-negative MPDs.
The classic myeloproliferative neoplasms (MPNs) include polycythemia vera and essential thrombocythemia; their molecular basis has been described only recently with the demonstration of recurrent mutations in JAK2 or MPL.
Thus, our findings indicate that differential expression of LGALS1 and/or LGALS3 in patients with MPN is linked with JAK2V617F status mutation in these diseases and state of cell differentiation.
Cytogenetic analysis seems to identify a subgroup of patients with a distinct prognostic profile, and should be performed in conjunction with a JAK2 mutation analysis in patients suspected of a chronic myeloproliferative disease.
TERT rs2736100_C and JAK2 GGCC are independently predisposing to MPN and have an additive effect on disease risk, together explaining a large fraction of the population attributable fraction (PAF = 73.06%).
Mutations of thrombopoietin, the thrombopoietin receptor (MPL), and the erythropoietin receptor and mutations of other genes involved in the pathogenesis of MPD were investigated in JAK2 wild-type patients.
To investigate the prevalence of calreticulin (CALR) mutations in JAK2- and MPL-non-mutated patients with suspected myeloproliferative neoplasm (MPN) from a large MPN clinic and confirm a diagnosis of MPN.
We conclude that the JAK2 1849G>T mutation is common in Ph(-) MPD but not critical for transformation to the acute phase of these diseases and that it is generally rare in aggressive leukemias.
The detection of the JAK2V617F mutation (c.1849GNT, GTC → TTC) is crucial for the diagnosis of myeloproliferative neoplasm (MPN) and has become the essential criteria for diagnosis of MPN by the WHO.
Furthermore, in this case, we believe that we are the first to demonstrate that JAK2 mutation in myeloid and B lymphoid cells but not T lymphocytes in a case of coexisting CLL and MPN.