Gender and Vascular Complications in the JAK2 V617F-Positive Myeloproliferative Neoplasms

Abstract

We previously found that gender influenced the JAK2 V617F allele burden, but it is unknown whether this gender difference in molecular epidemiology influences complications in the myeloproliferative neoplasms (MPNs). Historically, vascular complications represented the most common cause of mortality in polycythemia vera and essential thrombocytosis and contributed to morbidity in primary myelofibrosis. To determine the influence of gender on vascular complications, we retrospectively analyzed associations between gender and vascular complications. Despite their younger age, less prevalent dyslipidemia or smoking history, lower white blood counts, and lower JAK2 V617F allele burden, women had higher rates of abdominal venous thrombosis and comparable rates of all vascular complications. Vascular risk is currently not easily stratified by MPN-disease burden or traditional risk factors. Our analysis contributes to growing literature emphasizing gender differences in the MPN and further supports the important impact of individual and host variation on MPN clinical manifestations, and especially vascular risk.

MicroRNA deregulation in polycythemia vera and essential thrombocythemia patients

“…Consistent with the phenotypic and genotypic differences between male and female PV patients [31][32][33][34], there are different miRNA deregulations between male and female patients (Fig. 1).…”

“…Since erythrocytosis is the only feature that distinguishes PV from ET, we also compared specific miRNA expression in the nucleated erythroid cells directly descended from the burstforming unit erythroid (BFU-E) progenitor cells of PV and ET patients. Our data indicate that significant miRNA deregulation occurs in the CD34+ cells of PV patients and confirm a genetic basis for the gender-specific differences that characterize PV [31][32][33][34]. The results of our study also suggest that deregulated miRNAs may represent an important mechanism by which the PV erythrocytosis and ET thrombocytosis phenotypes are determined.…”

“…Given the phenotypic and genotypic differences between male and female PV patients [31][32][33][34], we analyzed differential miRNA expression separately by gender to identify genderspecific effects. Consistent with their different phenotypes, 79 miRNAs were differently regulated in the male PV patients (42 up and 37 down-regulated, p<0.05) compared to healthy male controls, while only 25 miRNAs were differently regulated in the female PV patients (9 up and 16 down-regulated, p<0.05) compared to healthy female controls.…”

Associations between gender, disease features and symptom burden in patients with myeloproliferative neoplasms: an analysis by the MPN QOL International Working Group

“…This is consistent with previous findings, with published data historically supporting a prevalence of females among ET patients and a prevalence of males among patients with PV. [13][14][15][16][17] Gender discrepancies within hematologic malignancies are not unique to MPN. Similar discordances in gender prevalence have been demonstrated in other disorders such as acute lymphoblastic leukemia, chronic lympho-…”

“…A recent investigation identified that women were more likely to experience macrothrombosis within the abdominal venous system (hepatic, portal, mesenteric or splenic veins) whereas males were more likely to experience events in the deep venous system, including limb thrombosis and pulmonary emboli. 16 Although the influence of gender on the pathogenesis of thrombosis remains unclear, mounting evidence suggests that both the type and ratio of circulating sex hormones plays an important role in the thrombotic cascade. In an investigation involving exogenous sex-steroid administration, ET patients exposed to hormone replacement therapy (estrogen only) had similar rates of arterial and venous thrombosis when compared to ET patients not on therapy.…”