The mammalian target of rapamycin (mTOR) critically regulates protein synthesis in response to microenvironmental cues and nutrients through its effector proteins 4E-BP1 and S6K,41 which are two important regulators of cap-dependent translation.42 Consistent with the observed increase in global translation, coculture with BMSCs promoted 4E-BP1 and S6K phosphorylation in both AML subtypes upon chemotherapy treatment combined with serum starvation (Figures S3C–S3H). Here, RPS6KB1 is linked to acute myeloid leukemia.