Combination of myeloproliferative neoplasm driver gene activation with mutations of splice factor or epigenetic modifier genes increases risk of rapid blastic progression.

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.