Heterozygosity for JAK2V617F Is a Risk Factor of Developing Post-Polycythemia Vera Myeloofibrosis?

Animal model studies report that heterozygous JAK2 V617F polycythemia vera (PV) has a low risk of progression to myelofibrosis. This clinical characteristic in humans is controversial. Therefore, we evaluated JAK2 V617F allele burden and myelofibrotic indicators such as reticulin level, bone marrow (BM) cellularity, CD34 levels and spleen size in 75 patients with heterozygous JAK2 V617F PV (45 males, 30 females, mean age 68 years) diagnosed according WHO criteria. Their mean duration of disease was 11 years (range, 1-26 years). All patients were on aspirin. The percentage of granulocyte mutant alleles was evaluated using a quantitative real-time polymerase chain reaction-based allelic discrimination assay. Reticulin level and BM cellularity were evaluated by ad hoc panel of 4 hematologists and 2 pathologists. CD34 levels were measured by flow cytometric assay. The spleen size was on ultrasound scan by measuring the longitudinal diameter (centimeters). Of 75 patients, 42 had allele burden > 10% (34±5%) (group 1) and 33 had allele burden < 10% (6±1%) (group 2). All patients had minor reticulin fibrosis (0.4±0.8), normal BM cellularity (76±8%), normal CD34 level (0.08±0.09%) whereas 24/42 (57%) of the group 1 and 3/33 (9%) of the group 2 had palpable splenomegaly (14±2.6 cm and 18 cm, respectively). These results suggest that heterozygosity > 10% might indicate a higher risk into the evolution of the so-called spent phase of the PV.