ASXL2 is essential for haematopoiesis and acts as a haploinsufficient tumour suppressor in leukemia.
作者： Jean-Baptiste Micol , Alessandro Pastore , Daichi Inoue , Nicolas Duployez , Eunhee Kim
DOI: 10.1038/NCOMMS15429
关键词:
摘要: Additional sex combs-like (ASXL) proteins are mammalian homologues of additional combs (Asx), a regulator trithorax and polycomb function in Drosophila. While there has been great interest ASXL1 due to its frequent mutation leukemia, little is known about paralog ASXL2, which frequently mutated acute myeloid leukemia patients bearing the RUNX1-RUNX1T1 (AML1-ETO) fusion. Here we report that ASXL2 required for normal haematopoiesis with distinct, non-overlapping effects from acts as haploinsufficient tumour suppressor. Asxl2 was haematopoietic stem cell self-renewal, loss promoted AML1-ETO leukemogenesis. Moreover, target genes strongly overlapped those RUNX1 associated increased chromatin accessibility at putative enhancers key leukemogenic loci. These data reveal critical mediates transcriptional promote leukemogenesis driven by AML1-ETO.
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