ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
miR-196b-TLR7/8 Signaling Axis Regulates Innate Immune Signaling and Myeloid Maturation in DNMT3A-Mutant AML.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Hyperprogressive disease in carcinoma induced by immune checkpoint inhibitor therapy: a systematic review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Pooled it
- Assessing the contributions of noncoding RNAs in acute myeloid leukemia.Blood neoplasia · 2026Review
- TLR2 agonism suppresses myeloid leukemogenesis by reprogramming leukemia stem cells.Blood advances · 2025Article
- Morphine Contributes to Epithelial-Mesenchymal Transition in Triple-Negative Breast Cancer Cells by Blocking COX-2 Methylation via Regulating the miR-23a-3p/DNMT3A Feedback.Cell biochemistry and biophysics · 2025Article
- TLR7/8 ligands R848 and imiquimod induce differentiation of bone marrow cells from patients with myelodysplastic syndrome towards mature neutrophils.Scientific reports · 2025Article
- Toll-Like Receptors in the Immunotherapy Era: Dual-Edged Swords of Tumor Immunity and Clinical Translation.MedComm · 2025Review
- Functions, mechanisms, and therapeutic implications of noncoding RNA in acute myeloid leukemia.Fundamental research · 2025Review
- Significance of targeting DNMT3A mutations in AML.Annals of hematology · 2025Review
- Gene Mutation Characteristics and Prognostic Significance in Acute Myeloid Leukemia Patients From Northeast China.Human mutation · 2025Article
- The interaction between common genetic mutations in AML and the immune landscape: mechanisms and implications for immune response.Frontiers in immunology · 2025Review
- Article
- Bone marrow inflammation in haematological malignancies.Nature reviews. Immunology · 2024Review
- Identification of Immunogenic Cell-Death-Related Subtypes and Development of a Prognostic Signature in Gastric Cancer.Biomolecules · 2023Article
- Noncoding rules of survival: epigenetic regulation of normal and malignant hematopoiesis.Frontiers in molecular biosciences · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
purposeDNMT3A 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. EXPERIMENTAL
designDNA 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.
resultsmiR-196b is hypomethylated and overexpressed in DNMT3A-mutant AML and is associated with poor patient outcome. miR-196b overexpression in DNMT3A-mutant AML is important to maintain an immature state and leukemic cell survival through repression of TLR signaling. The TLR7/8 agonist resiquimod induces dendritic cell-like differentiation with costimulatory molecule expression in DNMT3A-mutant AML cells and provides a survival benefit to Dnmt3a/Flt3-mutant AML mice. The small molecule bryostatin-1 augments resiquimod-mediated AML growth inhibition and differentiation.
conclusionsDNMT3A loss-of-function mutations cause miRNA locus-specific hypomethylation and overexpression important for mutant DNMT3A-mediated pathogenesis and clinical outcomes. Specifically, the overexpression of miR-196b in DNMT3A-mutant AML creates a novel therapeutic vulnerability by controlling sensitivity to TLR7/8-directed therapies.
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