ArticleClinical and translational medicine2022
CD44v6 chimeric antigen receptor T cell specificity towards AML with FLT3 or DNMT3A mutations.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 40 citations in OpenAlex.
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- The emerging roles of alternative splicing in modulating tumor immune responses and immunotherapies.Cell death and differentiation · 2026Review
- Next-generation CAR-T therapy for acute myeloid leukemia: bridging innovation with clinical translation.Annals of hematology · 2026Review
- Immunological barriers and engineering strategies for CAR-T cell therapy in acute myeloid leukemia.Frontiers in immunology · 2026Review
- Hotspots evolution and frontiers of immunotherapy for the treatment of acute myeloid leukemia: A bibliometric analysis.Human vaccines & immunotherapeutics · 2025Article
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- Emerging strategies and novel therapeutic targets in acute myeloid leukemia: current advances and future directions.Biomarker research · 2025Review
- CAR-T cell therapy for cancer: current challenges and future directions.Signal transduction and targeted therapy · 2025Review
- The Problem of Molecular Target Choice for CAR-T Cells in Acute Myeloid Leukemia Therapy.International journal of molecular sciences · 2025Review
- Novel strategy to target glioblastoma-initiating cells using a braintropic adeno-associated virus carrying a miR-dependent genome-editing system.British journal of cancer · 2025Article
- EVA1-antibody drug conjugate is a new therapeutic strategy for eliminating glioblastoma-initiating cells.Neuro-oncology · 2025Article
- Significance of targeting DNMT3A mutations in AML.Annals of hematology · 2025Review
- Precision medicine with car cells in acute myeloid leukemia: where are we?Frontiers in immunology · 2025Review
- Recent advances of chimeric antigen receptor T-cell therapy for acute myeloid leukemia.Frontiers in immunology · 2025Review
- Recent advances of CAR-T cells in acute myeloid leukemia.Therapeutic advances in hematology · 2025Review
- T cell-redirecting therapies in hematological malignancies: Current developments and novel strategies for improved targeting.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Recent Advances in Immune-Based Therapies for Acute Myeloid Leukemia.Blood cancer discovery · 2024Review
- Single-cell analysis of the survival mechanisms of fratricidal CAR-T targeting of T cell malignancies.Molecular therapy. Nucleic acids · 2024Article
- CD44 and its implication in neoplastic diseases.MedComm · 2024Review
- Recent advances in CAR-T cell therapy for acute myeloid leukaemia.Journal of cellular and molecular medicine · 2024Review
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Authors and funding
17 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChimeric antigen receptor T-cell (CAR-T) therapy for acute myeloid leukaemia (AML) has thus far been elusive, in part due to target restriction and phenotypic heterogeneity of AML cells. Mutations of the FMS-like tyrosine kinase 3 (FLT3) and DNA methyltransferase 3A (DNMT3A) genes are common driver mutations that present with a poor prognosis in AML patients. We found that AML patients with FLT3 or DNMT3A mutations had higher expression of CD44 isoform 6 (CD44v6) compared to normal specimens. Therefore, we intended to demonstrate CD44v6 could be a specific option for AML with FLT3 or DNMT3A mutations.
methodsInternal tandem duplication (ITD) mutations of FLT3 (FLT3/ITD) knock-in clone and DNMT3A-R882H mutant clones of SKM-1 cells were generated using CRISPR/Cas9 and lentiviral transfection, respectively. CD44v6 CAR-T cells were constructed by transfecting T cells with lentivirus containing CD44v6 CAR. CD44v6 expression in AML cell lines, AML patients and healthy donors was evaluated by flow cytometry. DNA methylation assays were used to analyse the mechanisms of FLT3 and DNMT3A mutations affecting CD44v6 expression.
resultsAberrant overexpression of CD44v6 was observed in AML cell lines with FLT3 or DNMT3A mutations compared to the wild-type SKM-1 or K562 cells. AML patients with FLT3 or DNMT3A mutations had higher expression of CD44v6 compared to normal specimens. Then we constructed CD44v6 CAR-T cells and found that CD44v6 CAR-T specifically lysed CD44v6
conclusionsCollectively, CD44v6 is a promising target of CAR-T for AML patients with FLT3 or DNMT3A mutations.
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