Methylation age as a correlate for allele burden, disease status and clinical response in myeloproliferative neoplasm patients treated with Vorinostat

The myeloproliferative neoplasms (MPNs) are a group of clonal hematological disorders, where there is a change from the polyclonal hematopoiesis seen in health, to an abnormal monoclonal proliferation of blood cells. Polycythemia vera (PV) and essential thrombocythemia (ET) are characterized respectively by the excess production of red blood cells and platelets. Identification of the JAK2 V617F driver mutation, in 95% of PV cases and 50% of ET cases, causing constitutive activation of the JAK/STAT pathway has revolutionized our understanding of the pathogenesis of these conditions.(1) In JAK2 V617F negative cases driver mutations in MPL and CALR have been identified in the majority of remaining ET cases.(2, 3) There is now evidence that MPNs are the result of combined genetic and epigenetic dysregulation, with mutations in co-operating genes increasingly reported.(4) These include genes involved in cell signalling pathways (LNK, CBL, NRA and, NF1), epigenetic regulation (ASXL1, EZH2, TET2, DNMT3A, IDH1 and IDH2), transcriptional regulation (TP53, RUNX1) and mRNA processing (SF3B1, SRSF2, U2AF1, ZRSR2).
Source: Experimental Hematology - Category: Hematology Authors: Source Type: research