biostudies-literatureUnknown9(19)Hou D<h4>Abstract</h4>In acute myeloid leukemia (AML), elevated interleukin 6 (IL-6) levels in the bone marrow (BM) are linked to poor prognosis. However, the mechanisms driving this elevation and its role in chemoresistance remain unclear. Using the Prrx1-Cre system, we selectively deleted Il6 in BM mesenchymal stromal cells (MSCs) and established an AML mouse model. Our results show that MSCs are a major source of IL-6 in AML BM. Importantly, Il6 deletion in MSCs reduced oxidative phosphorylation (OXPHOS) activity in AML cells, slowed disease progression, and enhanced chemosensitivity to cytarabine (Ara-C). Similarly, the OXPHOS inhibitor IACS-010759 improved chemosensitivity in AML mice. Exogenous recombinant IL-6 reversed the chemosensitivity gains from Il6 deletion, confirming its role in Blood advances4810-4824https://www.ebi.ac.uk/biostudies/studies/S-EPMC12495097biostudies-literatureTargeting bone marrow mesenchymal stromal cell-derived IL-6 to overcome acute myeloid leukemia chemoresistance.PMC12495097Fu QCai DLiu JTan MZheng XLiao XHuang HHou DDai WWang XWang JWang LfalseTargeting bone marrow mesenchymal stromal cell-derived IL-6 to overcome acute myeloid leukemia chemoresistance.<h4>Abstract</h4>In acute myeloid leukemia (AML), elevated interleukin 6 (IL-6) levels in the bone marrow (BM) are linked to poor prognosis. However, the mechanisms driving this elevation and its role in chemoresistance remain unclear. Using the Prrx1-Cre system, we selectively deleted Il6 in BM mesenchymal stromal cells (MSCs) and established an AML mouse model. Our results show that MSCs are a major source of IL-6 in AML BM. Importantly, Il6 deletion in MSCs reduced oxidative phosphorylation (OXPHOS) activity in AML cells, slowed disease progression, and enhanced chemosensitivity to cytarabine (Ara-C). Similarly, the OXPHOS inhibitor IACS-010759 improved chemosensitivity in AML mice. Exogenous recombinant IL-6 reversed the chemosensitivity gains from Il6 deletion, confirming its role in 2025-01-01T00:00:00Z2025 Oct2026-06-04T04:21:32.03Z2026-05-04T03:14:19.887ZS-EPMC124950974066861210.1182/bloodadvances.2024015496