Regulatory role of mTORC1 signaling in osteoblasts in acute myeloid leukemia progression and steady-state hematopoiesis.

ABSTRACT: Acute myeloid leukemia (AML) is widely recognized for its intrinsic leukemic-cell-driven regulation as well as its extrinsic niche-driven regulation. Despite mounting evidence that bone-forming osteoblasts provide an endosteal niche for AML cells, the precise mechanism remains to be elucidated. The cell-autonomous mammalian target of rapamycin complex 1 (mTORC1) is involved in the onset and progression of AML. Here, we found that mTORC1 signaling was activated in the osteoblasts of an AML murine model and clinical AML specimens. Osteoblast-specific mTORC1 activation in mice promotes AML growth, whereas mTORC1 inactivation suppresses it. Interleukin-6 (IL-6) was identified through screening as a downstream factor in mTORC1-regulated AML progression. Genetic ablation of the IL-6 receptor in

SUBMITTER: Fukasawa K 

PROVIDER: S-EPMC12808893 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature