Working model. In AML, HSPC-like leukemic cell populations exhibited one of two known chemoresistance-related expression signatures (LSC and OXPHOS) derived from mouse models (left panel). Among them, HSC-like leukemic cells characterized by the surface marker CD69 possessed chemoresistant capacity possibly via the CD69-mTOR axis. Suppression of the mTOR signaling pathway, in the CD69 + HSC-like cell subpopulation and CD69 -overexpressing cell lines, might lead to cell quiescence via suppression of cell cycle regulators CCND1 and CDK6 (as shown in Figs. 5 a and 6 b, and Fig. S5a) and cell adhesion to stromal cells such as MSCs through the CXCR4-CXCL12 interaction (as shown in Fig. 6 d, f). Patients with the CD69 + HSC-like subpopulation were associated with M0/M1 subtypes and specific genomic alterations and had worse clinical outcomes (right panel)
