biostudies-literatureGamlen HAAmerican Cancer SocietyNIDDK NIH HHSNational Institute of Diabetes and Digestive and Kidney DiseasesConcern FoundationNational Cancer InstituteNCI NIH HHSNational Institutes of HealthPennsylvania Department of Health4574-4586https://www.ebi.ac.uk/biostudies/studies/S-EPMC9588567biostudies-literatureUnknown28(20)<h4>Purpose</h4>DNMT3A mutations confer a poor prognosis in acute myeloid leukemia (AML), but the molecular mechanisms downstream of DNMT3A mutations in disease pathogenesis are not completely understood, limiting targeted therapeutic options. The role of miRNA in DNMT3A-mutant AML pathogenesis is understudied.<h4>Experimental design</h4>DNA methylation and miRNA expression was evaluated in human AML patient samples and in Dnmt3a/Flt3-mutant AML mice. The treatment efficacy and molecular mechanisms of TLR7/8-directed therapies on DNMT3A-mutant AML were evaluated in vitro on human AML patient samples and in Dnmt3a/Flt3-mutant AML mice.<h4>Results</h4>miR-196b is hypomethylated and overexpressed in DNMT3A-mutant AML and is associated with poor patient outcome. miR-196b overexpression in DNMTClinical cancer research : an official journal of the American Association for Cancer ResearchmiR-196b-TLR7/8 Signaling Axis Regulates Innate Immune Signaling and Myeloid Maturation in DNMT3A-Mutant AML.PMC9588567P30 CA056036R01 DK121831R37 CA226433T32 CA236736Romer-Seibert JSGamlen HALawler MEGuryanova OAGoetz MLFeng YMeyer SEPalmisiano NVersace AMfalsemiR-196b-TLR7/8 Signaling Axis Regulates Innate Immune Signaling and Myeloid Maturation in DNMT3A-Mutant AML.<h4>Purpose</h4>DNMT3A mutations confer a poor prognosis in acute myeloid leukemia (AML), but the molecular mechanisms downstream of DNMT3A mutations in disease pathogenesis are not completely understood, limiting targeted therapeutic options. The role of miRNA in DNMT3A-mutant AML pathogenesis is understudied.<h4>Experimental design</h4>DNA methylation and miRNA expression was evaluated in human AML patient samples and in Dnmt3a/Flt3-mutant AML mice. The treatment efficacy and molecular mechanisms of TLR7/8-directed therapies on DNMT3A-mutant AML were evaluated in vitro on human AML patient samples and in Dnmt3a/Flt3-mutant AML mice.<h4>Results</h4>miR-196b is hypomethylated and overexpressed in DNMT3A-mutant AML and is associated with poor patient outcome. miR-196b overexpression in DNMT2022-01-01T00:00:00Z2022 Oct2026-05-10T06:55:11.662Z2025-04-07T03:16:10.846ZS-EPMC95885673594329110.1158/1078-0432.CCR-22-159810.1158/1078-0432.ccr-22-1598