ArticleEMBO molecular medicine2024
Targeting the mevalonate or Wnt pathways to overcome CAR T-cell resistance in TP53-mutant AML cells.
Article in EMBO molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 25 citations in OpenAlex.
- Comparative efficacy and long-term survival of CD19/22 versus CD19 CAR-T immunotherapy in Relapsed/Refractory B-ALL with TP53 alterations.Journal of translational medicine · 2026Trial
- Preclinical advances and mechanistic insights of CAR-T therapy for acute myeloid leukemia: from target iteration to microenvironment regulation.Annals of medicine · 2026Review
- Pediatric AML CAR T cell therapy.Molecular therapy. Oncology · 2026Review
- TP53 deficiency in AML induces resistance to T-cell engagers through an immunosuppressive secretome.Leukemia · 2026Article
- Quantifying target antigen-dependent CAR T-cell performance against AML.Cancer cell international · 2026Article
- Targeting intracellular cholesterol imbalance rescues sarcomere-ER contact site signaling and ER remodeling in dilated cardiomyopathy.Signal transduction and targeted therapy · 2026Article
- Impact of TP53 alterations on outcomes in pediatric and young adult patients with relapsed / refractory B-cell acute lymphoblastic leukemia after CD19-CAR T-Cell therapy.Bone marrow transplantation · 2026Article
- Apolipoprotein B is considered a potential therapeutic drug target for the treatment of AML.Discover oncology · 2026Article
- Prime time for the use of statins in MPNs: from comorbidity drugs to disease-modifying partners.Blood advances · 2026Review
- Targeting immunoglobulin superfamily member 9 (IGSF9) to overcome acute myeloid leukemia resistance to CAR-T therapy.Journal of experimental & clinical cancer research : CR · 2026Article
- A Bispecific Anti-Fluorescein × Anti-CD3 T-cell Engager in Combination with Fluoresceinated Adaptors Enables Lysis of AML Cells.Molecular cancer therapeutics · 2026Article
- Biomarkers and advances in AML-MRC: from bench to bedside.Annals of hematology · 2026Review
- Review
- TP53-mutated myelodysplastic syndromes and acute myeloid leukemia: a comprehensive overview of targeted approaches.Frontiers in oncology · 2026Review
- Pandora's Box of AML: HowBiomedicines · 2025Review
- Review
- Molecular and Clinical Insights intoInternational journal of molecular sciences · 2025Review
- Targeting CD117 on hematopoietic stem and progenitor cells impairs CAR T cell activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- m6A hypermethylation of TCF-1 regulated by METTL16 promotes acute myeloid leukemia.Clinical and experimental medicine · 2025Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
TP53-mutant acute myeloid leukemia (AML) and myelodysplastic neoplasms (MDS) are characterized by chemotherapy resistance and represent an unmet clinical need. Chimeric antigen receptor (CAR) T-cells might be a promising therapeutic option for TP53-mutant AML/MDS. However, the impact of TP53 deficiency in AML cells on the efficacy of CAR T-cells is unknown. We here show that CAR T-cells engaging TP53-deficient leukemia cells exhibit a prolonged interaction time, upregulate exhaustion markers, and are inefficient to control AML cell outgrowth in vitro and in vivo compared to TP53 wild-type cells. Transcriptional profiling revealed that the mevalonate pathway is upregulated in TP53-deficient AML cells under CAR T-cell attack, while CAR T-cells engaging TP53-deficient AML cells downregulate the Wnt pathway. In vitro rational targeting of either of these pathways rescues AML cell sensitivity to CAR T-cell-mediated killing. We thus demonstrate that TP53 deficiency confers resistance to CAR T-cell therapy and identify the mevalonate pathway as a therapeutic vulnerability of TP53-deficient AML cells engaged by CAR T-cells, and the Wnt pathway as a promising CAR T-cell therapy-enhancing approach for TP53-deficient AML/MDS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.