biostudies-literatureLawler MENCI NIH HHS5888-5901https://www.ebi.ac.uk/biostudies/studies/S-EPMC12666352biostudies-literatureUnknown9(22)<h4>Abstract</h4>The consequences of activated innate immune signaling in acute myeloid leukemia (AML) is not well understood. Using ligands directed at the toll-like family receptors (TLR) in models of high-risk AML, we uncover that TLR2 ligands exert unique antileukemic effects that are distinct from other TLRs. Although TLR2 signaling broadly induces inflammatory gene expression in AML cells, at the single-cell level, cell-type-dependent, divergent transcriptional responses coordinate cellular outputs of proliferation, differentiation, cell death, and activation of immune cell function. TLR2 ligands were the only TLR agonists capable of extending survival of AML-bearing mice through leukemia stem cell (LSC) reprogramming that elevated major histocompatibility complex (MHC) class II surfBlood advancesTLR2 agonism suppresses myeloid leukemogenesis by reprogramming leukemia stem cells.PMC12666352F31 CA268843P30 CA056036R00 CA248460R37 CA226433R01 CA226432T32 CA236736Bowman MSRomer-Seibert JSLawler MEMeyer SEEischen CMBowman RLMitra RfalseTLR2 agonism suppresses myeloid leukemogenesis by reprogramming leukemia stem cells.<h4>Abstract</h4>The consequences of activated innate immune signaling in acute myeloid leukemia (AML) is not well understood. Using ligands directed at the toll-like family receptors (TLR) in models of high-risk AML, we uncover that TLR2 ligands exert unique antileukemic effects that are distinct from other TLRs. Although TLR2 signaling broadly induces inflammatory gene expression in AML cells, at the single-cell level, cell-type-dependent, divergent transcriptional responses coordinate cellular outputs of proliferation, differentiation, cell death, and activation of immune cell function. TLR2 ligands were the only TLR agonists capable of extending survival of AML-bearing mice through leukemia stem cell (LSC) reprogramming that elevated major histocompatibility complex (MHC) class II surf2025-01-01T00:00:00Z2025 Nov2026-07-15T06:57:44.943Z2026-06-30T03:34:43.103ZS-EPMC126663524083389110.1182/bloodadvances.2025017018