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Combination of myeloproliferative neoplasm driver gene activation with mutations of splice factor or epigenetic modifier genes increases risk of rapid blastic progression
Author(s) -
Bartels Stephan,
Vogtmann Julia,
Schipper Elisa,
Büsche Guntram,
Schlue Jerome,
Lehmann Ulrich,
Kreipe Hans
Publication year - 2021
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.13579
Subject(s) - essential thrombocythemia , myeloproliferative neoplasm , myelofibrosis , polycythemia vera , medicine , oncology , gene mutation , mutation , cancer research , gene , gastroenterology , genetics , biology , bone marrow
Objectives Myeloproliferative neoplasms (MPN) comprising polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) follow a bi‐phasic course of disease with fibrotic and/or blastic progression. At presentation in the chronic phase, currently there are only insufficient tools to predict the risk of progression in individual cases. Methods In this study, chronic phase MPN (16 PMF, 11 PV, and 11 MPN unclassified) with blastic transformation during course of disease (n = 38, median follow‐up 5.3 years) were analyzed by high‐throughput sequencing. MPN cases with a comparable follow‐up period and without evidence of blast increase served as control (n = 63, median follow‐up 5.8 years). Results Frequent ARCH/CHIP‐associated mutations ( TET2, ASXL1, DNMT3A ) found at presentation were not significantly associated with blastic transformation. By contrast, mutations of SRSF2, U2AF1 , and IDH1/2 at first presentation were frequently observed in the progression cohort (13/38, 34.2%) and were completely missing in the control group without blast transformation during follow‐up ( P = .0007 for SRSF2 ; P = .0063 for U2AF1 and IDH1/2 ). Conclusion Unlike frequent ARCH/CHIP alterations ( TET2, ASXL1, DNMT3A ), mutations in SRSF2, IDH1/2 , and U2AF1 when manifest already at first presentation provide an independent risk factor for rapid blast transformation of MPN.