| First Author | Fukasawa K | Year | 2026 |
| Journal | iScience | Volume | 29 |
| Issue | 1 | Pages | 114533 |
| PubMed ID | 41550719 | Mgi Jnum | J:378670 |
| Mgi Id | MGI:8280147 | Doi | 10.1016/j.isci.2025.114533 |
| Citation | Fukasawa K, et al. (2026) Regulatory role of mTORC1 signaling in osteoblasts in acute myeloid leukemia progression and steady-state hematopoiesis. iScience 29(1):114533 |
| abstractText | 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 AML cells significantly attenuated AML growth in osteoblast-specific mTORC1-activated mice. Collectively, our results suggest that the mTORC1/IL-6 axis in osteoblastic niche non-autonomously contributes to the AML progression, suggesting a viable therapeutic target for AML. |
