Homeobox Transcription Factor Hhex Promotes Myeloid Leukemia In Cooperation With Mutant Asxl1

Additional sex combs-like 1 (ASXL1) mutations are frequently found in myeloid malignancies such as AML, MDS and MPNs. Our previous study on mutant Asxl1 expressing knock-in (Asxl1-MT KI) mice revealed that Asxl1-MT impaired normal hematopoiesis (Nagase R et al. J. Exp. Med. 2018). However, Asxl1-MT alone was insufficient to develop myeloid leukemia. Thus, additional factors are required for myeloid transformation in ASXL1-mutated cells. Retrovirus-mediated insertional mutagenesis approaches demonstrated susceptibility of Asxl1-MT KI cells to myeloid leukemia, and helped identifying Hematopoietically expressed homeobox (Hhex) gene as a common retrovirus integration site. Therefore, we here investigated the potential cooperation between ASXL1-MT and HHEX in myeloid leukemogenesis.