ArticleCancer cell2023
Modulation of RNA splicing enhances response to BCL2 inhibition in leukemia.
Article in Cancer cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 74 citations in OpenAlex.
- Dynamic Switching of Apoptosis-Modulating Bim Heterodimers in Response to BH3 Mimetics in Xenograft Models of Hematologic Malignancies.Molecular cancer therapeutics · 2026Article
- PTBP1 controls oncogenic transcript processing and maintenance of acute myeloid leukemia.Leukemia · 2026Article
- RNA splicing in health and disease.Molecular biomedicine · 2026Review
- Inhibition of PRMT5 sensitizes B-cell non-Hodgkin lymphoma cells to both intrinsic and extrinsic apoptotic cell death.Blood neoplasia · 2026Article
- U2 snRNP inhibition hampers pancreatic cancer cell viability by disrupting DNA repair proficiency and mitotic checkpoint integrity.Journal of experimental & clinical cancer research : CR · 2026Article
- Acute Myeloid Leukemia with Myelodysplasia-Related Gene Mutations.Journal of clinical medicine · 2026Review
- Splicing-associated network PAK1-CLK1/4-SRRM1 is a vulnerability to overcome chemoresistance in human and mouse acute myeloid leukemia.Science translational medicine · 2026Article
- The emerging roles of alternative splicing in modulating tumor immune responses and immunotherapies.Cell death and differentiation · 2026Review
- Dual FLT3/PIM inhibitor dapolsertib in acute myeloid leukemia: results from the phase 1/2 DIAMOND-01 trial.Blood neoplasia · 2026Article
- Elucidating the mechanisms of bisphenols-induced male spermatogenesis disorder via network toxicology, molecular docking and bioinformatics.BMC medical genomics · 2026Article
- Phase 1 study of rogocekib in patients with relapsed or refractory hematologic malignancies.Blood advances · 2026Article
- More than CLK bait? Rogocekib for MDS and AML.Blood advances · 2026Article
- RNA Splicing as a Therapeutic Target in Cancer.Annual review of pharmacology and toxicology · 2026Review
- Precision prediction of venetoclax-azacitidine treatment efficacy in acute myeloid leukemia via integrative drug screening and machine learning.Cell reports. Medicine · 2025Article
- Meeting Report From the 2024 Symposium on IRAK4 in Cancer: Highlights and Clinical Updates.Clinical lymphoma, myeloma & leukemia · 2025Review
- Splicing Factor Mutations in Chronic Myelomonocytic Leukemia: Biological Consequences and Therapeutic Implications.Current hematologic malignancy reports · 2025Review
- Comparable Short Term Outcomes Among Patients with Newly Diagnosed Acute Myeloid Leukemia with or without Myelodysplasia Related Gene Mutations Treated with Azacytidine-Venetoclax: Observations from a Single Center Retrospective Cohort.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2025Article
- An Isoform-Specific RUNX1C-BTG2 Axis Governs AML Quiescence and Chemoresistance.Blood cancer discovery · 2025Article
- Targeting HASPIN kinase disrupts SR protein-mediated RNA splicing and synergizes with BCL-2 inhibitor venetoclax in AML.Blood neoplasia · 2025Article
- RBM10 loss promotes metastases by aberrant splicing of cytoskeletal and extracellular matrix mRNAs.The Journal of experimental medicine · 2025Article
Corrections and comments
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Authors and funding
27 authors at 4 institutions in 1 country.
Funding
Abstract
Therapy resistance is a major challenge in the treatment of cancer. Here, we performed CRISPR-Cas9 screens across a broad range of therapies used in acute myeloid leukemia to identify genomic determinants of drug response. Our screens uncover a selective dependency on RNA splicing factors whose loss preferentially enhances response to the BCL2 inhibitor venetoclax. Loss of the splicing factor RBM10 augments response to venetoclax in leukemia yet is completely dispensable for normal hematopoiesis. Combined RBM10 and BCL2 inhibition leads to mis-splicing and inactivation of the inhibitor of apoptosis XIAP and downregulation of BCL2A1, an anti-apoptotic protein implicated in venetoclax resistance. Inhibition of splicing kinase families CLKs (CDC-like kinases) and DYRKs (dual-specificity tyrosine-regulated kinases) leads to aberrant splicing of key splicing and apoptotic factors that synergize with venetoclax, and overcomes resistance to BCL2 inhibition. Our findings underscore the importance of splicing in modulating response to therapies and provide a strategy to improve venetoclax-based treatments.
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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.