Gender Is A Phenotypic Modifier In The Jak2 V617f-Positive Mpd

Introduction: The myeloproliferative disorders (MPD), essential thrombocytosis (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) share the same acquired genetic lesion, JAK2V617F, but differ with respect to epidemiology, natural history and gender. We have shown that the JAK2V617F allele burden at both the neutrophil and CD34+ cell level varies amongst MPD patients, and is a consequence of both the degree of dominance of the JAK2V617F clone and the specific JAK2V617F genotype (heterozygous versus homozygous) of the disease clones. The variability of the JAK2V617F expression, which in some female ET patients is restricted to platelets only, is a major modifier of MPD disease class and within PV, a modifier of white cell count and extramedullary disease. We hypothesized that gender may be an important modifier of the JAK2V617F burden and, therefore, the disease phenotype, and examined the relationship between gender, disease phenotype and the quantitative JAK2V617F allele burden in both CD34+ cells and neutrophils in JAK2V617F -positive MPD patients.