JAK2V617F monitoring in polycythemia vera and essential thrombocythemia: Clinical usefulness for predicting myelofibrotic transformation and thrombotic events

Abstract

The JAK2V617F allele burden has been identified as a risk factor for vascular events and myelofibrotic transformation in polycythemia vera (PV) and essential thrombocythemia (ET). However, all previous studies have evaluated a single time point JAK2V617F measurement. Therefore, the frequency and the clinical significance of changes in the JAK2V617F mutant load occurring during the disease evolution remain unknown. In the present study, JAK2V617F monitoring was performed during the follow‐up of 347 patients (PV = 163, ET = 184). According to their JAK2V617F evolutionary patterns, patients were stratified as stable < 50% (n = 261), stable ≥50% (n = 52), progressive increase (n = 24) and unexplained decrease (n = 10). After a 2,453 person‐years follow‐up, a total of 59 thrombotic events, 16 major hemorrhages, and 27 cases of myelofibrotic transformations were registered. At multivariate analyses, patients with a persistently high (≥50%) or unsteady JAK2V617F load during follow‐up had an increased risk of myelofibrotic transformation (Incidence rate ratio [IRR]: 20.7, 95% CI: 6.5–65.4; P < 0.001) and a trend for a higher incidence of thrombosis (IRR: 1.7, 1–3.3; P = 0.05) than patients with a stable allele burden below 50%. In conclusion, JAK2V617F monitoring could be useful in patients with PV and ET for predicting disease's complications, especially myelofibrotic transformation. Am. J. Hematol. 89:517–523, 2014. © 2014 Wiley Periodicals, Inc.

Mutations in MPNs: prognostic implications, window to biology, and impact on treatment decisions

“…In particular, homozygous allele burden has been associated with older age, male sex, pruritus, and splenomegaly; associations between homozygous or increasing allelic burdens and thrombosis (arterial and venous), as well as MF transformation have also been suggested. [24][25][26][27][28][29] Another well recognized phenotypic association with JAK2 V617F includes hepatic and portal vein thrombosis, but affected patients present a unique exception with regard to demographics, clinical phenotype, and allelic burden, because this complication is often observed in younger women, with either a masked phenotype, or lower leukocyte counts and lower allelic burdens. 30,31 Mutations involving MPL, JAK2 exon 12, and CALR are infrequently identified relative to JAK2 V617F in patients presenting with abdominal vein thrombosis.…”

How I treat polycythemia vera

“…However, in patients that are suspected to evolve to post-PV myelofibrosis (PPV-MF), I repeat the test to document accumulation of mutated alleles that usually accompanies transition to PPV-MF. [25][26][27][28] At present, there is no evidence that assessing other MPN-associated mutations 14 provides prognostic information, unlike in PMF patients. [29][30][31] I routinely order quantification of serum erythropoietin (sEPO) levels before phlebotomy is started to avoid fluctuations.…”

Incidence and risk factors for myelofibrotic transformation among 272 Chinese patients with JAK2-mutated polycythemia vera

“…In addition, increases in circulating blast cells and WBC count were not associated with poor prognosis of post-PV MF. The present study also JAK2 mutation V617F is detected in approximately 91-95% of patients with PV [14][15][16][17], and the effect of mutant allele burden on the clinical phenotype and severity of PV has also been extensively studied [24][25][26][27][28][29][30]. Previous studies have also shown that the incidence of post-PV MF was significantly higher in patients with V617F%…”