Focus on the epigenome in the myeloproliferative neoplasms

摘要

The discovery of mutations activating JAK-STAT signaling in the majority of patients with myeloproliferative neoplasms (MPNs) led to identification of tyrosine kinase activation as a predominant mechanism driving MPN pathogenesis. Despite this, the existence of additional genetic events that modify the MPN phenotype, predate JAK2 mutations, and/or contribute to leukemic transformation of MPNs has been suggested. Recently, mutations in several epigenetic modifiers have been described in patients with MPNs, including mutations in ASXL1 , DNMT3A , EZH2 , IDH1 , IDH2 , and TET2 . Moreover, the mutant JAK2 itself has been shown recently to affect histone posttranslational modifications directly. Here we review the biological and clinical implications of epigenetic alterations in the pathogenesis of MPNs.