Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by the clonal expansion of immature myeloid cells. There is an urgent and unmet need for the development of novel therapeutics against AML. Autophagy is a lysosomal catabolic process that has been implicated in leukemia cell survival and chemotherapy response. However, the biological role of autophagy in AML leukemogenesis remains poorly defined. In this study, we genetically ablated ATG5, a gene that is essential for autophagy, in AML cells during leukemogenesis in a murine model of MLL-AF9-driven AML. The homozygous deletion of ATG5 in AML cells significantly delayed MLL-AF9-induced leukemogenesis and progression in vivo. Likewise, the in vitro deletion of ATG5 in MLL-AF9 driven AML cells demonstrated decreased growth as well as reduced colony forming units. Interestingly, ATG5 deficiency demonstrated an altered differentiation hierarchy of MLL-AF9-induced AML cells in vivo that could be linked to decreased proliferation and suppressed leukemogenesis. Overall, this study provides insight at how autophagy can facilitate AML progression. A more comprehensive understanding on autophagy in AML is needed prior to the deployment of autophagy modulators for the treatment of AML.
Citation Format: Qiang Liu, Longgui Chen, Hong-Gang Wang. Autophagy facilitates leukemogenesis in a murine model of MLL-AF9-driven AML. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3531.