ArticleThe Journal of clinical investigation2023
SF3B1 mutation and ATM deletion codrive leukemogenesis via centromeric R-loop dysregulation.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- RNA splicing in health and disease.Molecular biomedicine · 2026Review
- Spliceosomal mutation drives melanoma tumorigenesis via lineage-specific RAS activation.Science advances · 2026Article
- Cancer-associated SF3B1 mutation suppresses DNA repair by disrupting the organization of nuclear actin network.Cell death & disease · 2026Article
- Vulnerability of SRSF2-mutated chronic myelomonocytic leukemia to perturbation of the cGAS-STING pathway.Blood advances · 2026Article
- DIS3 licenses B cells for plasma cell differentiation in humans.Cellular & molecular immunology · 2026Article
- Atypical R-loops in cancer: decoding molecular chaos for therapeutic gain.Journal of translational medicine · 2025Review
- USP15 Drives NSCLC Progression and Chemoresistance, Potentially via Regulation of the U2-Type Spliceosomal Complex.Cancer medicine · 2025Article
- Review
- Insights into genetic aberrations and signalling pathway interactions in chronic lymphocytic leukemia: from pathogenesis to treatment strategies.Biomarker research · 2024Review
- Steering research on mRNA splicing in cancer towards clinical translation.Nature reviews. Cancer · 2024Review
- Nucleolar Pol II interactome reveals TBPL1, PAF1, and Pol I at intergenic rDNA drive rRNA biogenesis.Nature communications · 2024Article
- Molecular impact of mutations in RNA splicing factors in cancer.Molecular cell · 2024Review
- Cancer-associated SF3B1-K700E mutation controls immune responses by regulating TScience advances · 2024Article
- Mis-splicing of Mitotic Regulators Sensitizes SF3B1-Mutated Human HSCs to CHK1 Inhibition.Blood cancer discovery · 2024Article
- Engineering Oncogenic Hotspot Mutations on SF3B1 via CRISPR-Directed PRECIS Mutagenesis.Cancer research communications · 2024Article
- RNA biogenesis and RNA metabolism factors as R-loop suppressors: a hidden role in genome integrity.Genes & development · 2024Review
- Non-canonical role for the BAF complex subunit DPF3 in mitosis and ciliogenesis.Journal of cell science · 2024Article
- The molecular map of CLL and Richter's syndrome.Seminars in hematology · 2024Review
- Germline Variants and Characteristic Features of Hereditary Hematological Malignancy Syndrome.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
RNA splicing factor SF3B1 is recurrently mutated in various cancers, particularly in hematologic malignancies. We previously reported that coexpression of Sf3b1 mutation and Atm deletion in B cells, but not either lesion alone, leads to the onset of chronic lymphocytic leukemia (CLL) with CLL cells harboring chromosome amplification. However, the exact role of Sf3b1 mutation and Atm deletion in chromosomal instability (CIN) remains unclear. Here, we demonstrated that SF3B1 mutation promotes centromeric R-loop (cen-R-loop) accumulation, leading to increased chromosome oscillation, impaired chromosome segregation, altered spindle architecture, and aneuploidy, which could be alleviated by removal of cen-R-loop and exaggerated by deletion of ATM. Aberrant splicing of key genes involved in R-loop processing underlay augmentation of cen-R-loop, as overexpression of the normal isoform, but not the altered form, mitigated mitotic stress in SF3B1-mutant cells. Our study identifies a critical role of splice variants in linking RNA splicing dysregulation and CIN and highlights cen-R-loop augmentation as a key mechanism for leukemogenesis.
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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.