Akihide Yoshimi, Kuan-Ting Lin, Daniel H Wiseman, Mohammad Alinoor Rahman, Alessandro Pastore, Bo Wang, Stanley Chun-Wei Lee, Jean-Baptiste Micol, Xiao Jing Zhang, Stephane de Botton, Virginie Penard-Lacronique, Eytan M Stein, Hana Cho, Rachel E Miles, Daichi Inoue, Todd R Albrecht, Tim C P Somervaille, Kiran Batta, Fabio Amaral, Fabrizio Simeoni, Deepti P Wilks, Catherine Cargo, Andrew M Intlekofer, Ross L Levine, Heidi Dvinge, Robert K Bradley, Eric J Wagner, Adrian R Krainer, Omar Abdel-Wahab
Transcription and pre-mRNA splicing are key steps in the control of gene expression and mutations in genes regulating each of these processes are common in leukaemia1,2 . Despite the frequent overlap of mutations affecting epigenetic regulation and splicing in leukaemia, how these processes influence one another to promote leukaemogenesis is not understood and, to our knowledge, there is no functional evidence that mutations in RNA splicing factors initiate leukaemia. Here, through analyses of transcriptomes from 982 patients with acute myeloid leukaemia, we identified frequent overlap of mutations in IDH2 and SRSF2 that together promote leukaemogenesis through coordinated effects on the epigenome and RNA splicing...
October 2, 2019: Nature