Fig. 1. Main mutations identified in Myeloproliferative Neoplasms.

MPNs are characterized by acquired mutations in genes controlling various cellular processes (yellow boxes), all involved in different steps of the gene expression regulation. The receptors of erythropoïetin (EPO-R) or of thrombopoïetin (MPL) are constitutively associated to the JAK2 kinase. The driver mutations initiating the disease (marked by red stars) target either JAK2, CALR or MPL genes, all three resulting in an activation of the JAK/STAT and RAS pathways. Additional mutations (marked by yellow stars) may be acquired before or after the driver mutation and can accumulate during disease evolution. Such mutations have been identified in genes involved in epigenetics (TET2, ASXL1, DNMT3A, EZH2 or IDH1/2), mRNA splicing (SRSF2, SF3B1, U2AF1, ZRSR2), cell signalling (NRAS, KRAS, CBL, SH2B3 coding for LNK protein) or factors regulating the transcription (NFE2, TP53). Of note, mutations targeting PTPN11, NGAS, SETBP1, NF1 (signalling) or RUNX1, ETV6, CUX1, STAG2, PHF6, BCOR, BCORL1 (transcription regulation) have also been reported (but less frequently) in MPN patients [2–4].