Targeting bone marrow mesenchymal stromal cell-derived IL-6 to overcome acute myeloid leukemia chemoresistance.

ABSTRACT:

Abstract

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

SUBMITTER: Hou D 

PROVIDER: S-EPMC12495097 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature