ArticleJCI insight2018
Splicing modulation sensitizes chronic lymphocytic leukemia cells to venetoclax by remodeling mitochondrial apoptotic dependencies.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- Inhibition of PRMT5 sensitizes B-cell non-Hodgkin lymphoma cells to both intrinsic and extrinsic apoptotic cell death.Blood neoplasia · 2026Article
- Splicing-associated network PAK1-CLK1/4-SRRM1 is a vulnerability to overcome chemoresistance in human and mouse acute myeloid leukemia.Science translational medicine · 2026Article
- Proteogenomic features define subtypes of mantle cell lymphoma.Blood advances · 2026Article
- Tonic signaling of the B-cell antigen-specific receptor is a common functional hallmark in chronic lymphocytic leukemia cell phosphoproteomes at early disease stages.Molecular oncology · 2025Article
- Eμ-TCL1 mice with conditional human BCL2 knockin as novel B-cell lymphoma model for studying venetoclax effects in vivo.Blood neoplasia · 2025Article
- Enitociclib, a selective CDK9 inhibitor: in vitro and in vivo preclinical studies in multiple myeloma.Blood neoplasia · 2025Article
- LP-118 is a novel B-cell lymphoma 2 / extra-large inhibitor that demonstrates efficacy in models of venetoclaxresistant chronic lymphocytic leukemia.Haematologica · 2025Article
- SF3B1K700E mutation in human embryonic stem cells causes aberrant expression of immune-related genes.PloS one · 2025Article
- Venetoclax dose escalation rapidly activates a BAFF/BCL-2 survival axis in chronic lymphocytic leukemia.Blood · 2024Article
- The prognostic significance of genetics in acute myeloid leukemia under venetoclax-based treatment.Annals of hematology · 2024Review
- Targeting splicing for hematological malignancies therapy.BMC genomics · 2024Review
- Article
- The Impact of Spliceosome Inhibition in SF3B1-Mutated Uveal Melanoma.Investigative ophthalmology & visual science · 2024Article
- Integrative Analysis of Multi-Omics Data to Identify Deregulated Molecular Pathways and Druggable Targets in Chronic Lymphocytic Leukemia.Journal of personalized medicine · 2024Article
- Splicing modulators impair DNA damage response and induce killing of cohesin-mutant MDS and AML.Science translational medicine · 2024Article
- Article
- Posttranslational splicing modifications as a key mechanism in cytarabine resistance in acute myeloid leukemia.Leukemia · 2023Article
- METTL3-Mediated m6A Modification Controls Splicing Factor Abundance and Contributes to Aggressive CLL.Blood cancer discovery · 2023Article
- Global Shift in Alternative Splicing and Therapeutic Susceptibilities in Leukemia Driven by METTL3 Overexpression.Blood cancer discovery · 2023Article
- Review
Corrections and comments
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Authors and funding
30 authors.
Funding
Abstract
The identification of targetable vulnerabilities in the context of therapeutic resistance is a key challenge in cancer treatment. We detected pervasive aberrant splicing as a characteristic feature of chronic lymphocytic leukemia (CLL), irrespective of splicing factor mutation status, which was associated with sensitivity to the spliceosome modulator, E7107. Splicing modulation affected CLL survival pathways, including members of the B cell lymphoma-2 (BCL2) family of proteins, remodeling antiapoptotic dependencies of human and murine CLL cells. E7107 treatment decreased myeloid cell leukemia-1 (MCL1) dependence and increased BCL2 dependence, sensitizing primary human CLL cells and venetoclax-resistant CLL-like cells from an Eμ-TCL1-based adoptive transfer murine model to treatment with the BCL2 inhibitor venetoclax. Our data provide preclinical rationale to support the combination of venetoclax with splicing modulators to reprogram apoptotic dependencies in CLL for treating venetoclax-resistant CLL cases.
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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.