ArticleBlood advances2021
Mesothelin is a novel cell surface disease marker and potential therapeutic target in acute myeloid leukemia.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Review
- The search for safe and effective CAR-T targets in AML.Blood cancer journal · 2026Review
- MSLN expression predicts a high risk of EMD in AML by promoting cell adhesion and metastasis via interaction with MUC16.Blood advances · 2026Article
- Mesothelin Expression in Acute Leukemia: Correlations With Immunophenotype, Cytogenetics, and Mutational Status.Applied immunohistochemistry & molecular morphology : AIMM · 2026Article
- Mesothelin promotes acute myeloid leukemia progression through LYN-dependent signaling.The Journal of biological chemistry · 2026Article
- Mesothelin biology and the evolving landscape of targeted immunotherapy.Molecular therapy. Oncology · 2026Review
- Novel perspectives on MSLN-targeted cancer therapy: from molecular mechanisms to clinical translation.Cancer biology & therapy · 2025Review
- Mesothelin as a biomarker and potential therapeutic target in rheumatoid arthritis bone destruction.Cell reports. Medicine · 2025Article
- CD33Journal for immunotherapy of cancer · 2025Article
- Dual targeting of tumoral cells and immune microenvironment by blocking the IL-33/IL1RL1 pathway.Nature communications · 2025Article
- Potent and durable control of mesothelin-expressing tumors by a novel T cell-secreted bi-specific engager.Journal for immunotherapy of cancer · 2025Article
- Advances in the application of patient-derived xenograft models in acute leukemia resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Rational combinatorial targeting by adapter CAR-T-cells (AdCAR-T) prevents antigen escape in acute myeloid leukemia.Leukemia · 2024Article
- Review
- Enhanced Expression of Glycolytic Enzymes and Succinate Dehydrogenase Complex Flavoprotein Subunit A by Mesothelin Promotes Glycolysis and Mitochondrial Respiration in Myeloblasts of Acute Myeloid Leukemia.International journal of molecular sciences · 2024Article
- A CD8Frontiers in immunology · 2024Article
- The 4-1BBζ costimulatory domain in chimeric antigen receptors enhances CD8+ T-cell functionality following T-cell receptor stimulation.Cancer cell international · 2023Article
- Relapsed pediatric acute myeloid leukaemia: state-of-the-art in 2023.Haematologica · 2023Review
- Review
- Pediatric Myeloid Sarcoma, More than Just a Chloroma: A Review of Clinical Presentations, Significance, and Biology.Cancers · 2023Review
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Authors and funding
21 authors at 7 institutions in 1 country.
Funding
Abstract
In an effort to identify acute myeloid leukemia (AML)-restricted targets for therapeutic development in AML, we analyzed the transcriptomes of 2051 children and young adults with AML and compared the expression profile with normal marrow specimens. This analysis identified a large cohort of AML-restricted genes with high expression in AML, but low to no expression in normal hematopoiesis. Mesothelin (MSLN), a known therapeutic target in solid tumors, was shown to be highly overexpressed in 36% of the AML cohort (range, 5-1077.6 transcripts per million [TPM]) and virtually absent in normal marrow (range, 0.1-10.7 TPM). We verified MSLN transcript expression by quantitative reverse transcription polymerase chain reaction, confirmed cell surface protein expression on leukemic blasts by multidimensional flow cytometry, and demonstrated that MSLN expression was associated with promoter hypomethylation. MSLN was highly expressed in patients with KMT2A rearrangements (P < .001), core-binding factor fusions [inv(16)/t(16;16), P < .001; t(8;21), P < .001], and extramedullary disease (P = .001). We also demonstrated the presence of soluble MSLN in diagnostic serum specimens using an MSLN-directed enzyme-linked immunosorbent assay. In vitro and in vivo preclinical efficacy of the MSLN-directed antibody-drug conjugates (ADCs) anetumab ravtansine and anti-MSLN-DGN462 were evaluated in MSLN+ leukemia cell lines in vitro and in vivo, as well as in patient-derived xenografts. Treatment with ADCs resulted in potent target-dependent cytotoxicity in MSLN+ AML. In this study, we demonstrate that MSLN is expressed in a significant proportion of patients with AML and holds significant promise as a diagnostic and therapeutic target in AML, and that MSLN-directed therapeutic strategies, including ADCs, warrant further clinical investigation.
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