VEGFA rs3025039 is associated with phenotype severity of myelofibrosis‐type megakaryocyte dysplasia

Abstract

ABL-negative myeloproliferative neoplasms (MPNs) include the World Health Organization (WHO) defined classical MPNs, that is essential thrombocythaemia, polycythaemia vera (PV) and primary myelofibrosis (PMF). Recently, two new cognate phenotypes, that is, clonal megakaryocyte dysplasia with normal blood values (CMD-NBV), and clonal megakaryocyte dysplasia with isolated thrombocytosis (CMD-IT) have been proposed [1, 2]. These entities, along with prefibrotic myelofibrosis (pre-MF) and overt-MF were unified by bone marrow (BM) myelofibrosis-type megakaryocyte dysplasia (MTMD) [3]. Myeloproliferation in MPNs is driven by gain-of-function mutations in JAK2, CALR or MPL genes. Persons with these mutations may have additional mutations common to other myeloid cancers including ASXL1, EZH2, DMNT3A, IDH1 and IDH2. However, these divergent genotypes do not completely account for different MPN phenotypes and new explanations are sought. Single nucleotide variations (SNVs) are a possible explanation for this phenotypic heterogeneity. Three common SNVs of VEGFA, that is, rs2010963, rs3025020 and rs3025039, influence predisposition, phenotype, and risk of thrombosis in subjects with PMF [4-6]. We interrogated a possible association between the VEGFA SNVs and variant phenotypes in the MTMD category. We analyzed stored DNA from blood granulocytes of 857 consecutive subjects seen at the Center for the Study of Myelofibrosis of the IRCCS Policlinico S.