Signal transducers and activators of transcription 3 (STAT3) analysis of a small group of ET patients shows that in about half of the patients, there is STAT3 hyperactivation independently of JAK2 mutations, suggesting that the hyperactivation of STAT3 by JAK2 mutations or promoter activation may be a critical step in development of ET.
Retrospective data have identified JAK2(V617F) as a risk factor for thrombosis in ET, and have also shown a close association with abdominal vein thrombosis.
Finally, a significant correlation between JAK2 V617F mutational status and hematocrit (Ht), white blood cell and platelet counts in PV patients, and Ht values in ET cases, was observed by AS-PCR.
"The significance of bone marrow biopsy and JAK2V617F mutation in the differential diagnosis between the ""early"" prepolycythemic phase of polycythemia vera and essential thrombocythemia."
These findings suggest that the JAK2 V617F mutation is not rare in childhood sporadic ET cases, and that these cases might be older and myeloproliferative features.
In this single-center retrospective study, JAK2(V617F) allele load was measured by sensitive quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in the granulocytes of 260 patients diagnosed as having essential thrombocythemia according to WHO criteria.
Based on the hypothesis that JAK-STAT signaling is central to the pathogenesis of JAK2V617F-negative MPN, genomic studies have identified JAK2 exon 12 mutations in JAK2V617F-negative PV and activating mutations in MPL in patients with JAK2V617F-negative ET and PMF.
The rate of thrombotic complications in JAK2-positive ET patients was significantly higher than that in wild-type ET patients and not statistically different from that in PV patients.
We conclude that megakaryocytes might be the predominant or even the exclusive lineage that acquires the JAK2(V617F) mutation in ET and that the JAK2(V617F) evolution to higher gene dosages represents a dynamic and complex process substantially involving megakaryocytes.
Accordingly, the WHO concept of two distinct entities, ET and prefibrotic IMF, does not seem to fit the model of JAK2-positive ET as part of a biological continuum of JAK2 V617F-positive chronic myeloproliferative disorders.
A single point mutation (Val617Phe) was identified in JAK2 in 42 (73.7%) of 57 patients with PV, 40 (58.8%) of 68 with ET, and eight (66.7%) of 12 with MMM.
We analyzed the expression of AGT, renin, AT2R1 and ACE genes in normal and bone marrows of PV and ET patients with the respect to the presence of V617F JAK2 mutation.