Autophagy-deficient mice are more susceptible to engrafted leukemogenesis

Autophagy is primarily considered as an important survival mechanism for both normal cells and cancer cells in response to metabolic stress or chemotherapy; but the role of autophagy in leukemogenesis is not fully understood. The aim of this study is to explore the role of intrinsic autophagy in the leukemogenesis of B-cell acute lymphoblastic leukemia (B-ALL). In this study, conditional knockout mice Atg7^f/f;Ubc-Cre, in which an autophagy-essential gene Atg7 is universally deleted, were used as recipients, B-ALL cell line 697 was used as donor cells to generate leukemia mouse model. Compared to wild-type mice, Atg7 knockout mice were more susceptible to engrafted leukemogenesis, shown by increase in white blood cells, lymphocytes, and platelets, decrease in HSPC number and its colony-forming unit (CFU). The liver and spleen displayed hepatosplenomegaly and inflammatory cell infiltration. Furthermore, second competitive transplantation revealed dysfunction of the HSPC in Atg7-knockout leukemia mice represented by destructive self-renew ability (CFU) and reconstitution ability including decreased B220, Ter 119 cells, and increased Gr-1 cell percentage. In summary, Mice with universal deletion of Atg7 are more inclined to the occurrence of engrafted human leukemia, which is largely attributed to the deterioration of the function of HSPC in autophagy deficient mice.