ArticleCancer cell2018
Synthetic Lethal and Convergent Biological Effects of Cancer-Associated Spliceosomal Gene Mutations.
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Article in Cancer cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers.
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154citing papers in PubMed
9.5field-weighted citation impact, top 1% of its field
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Who cites it
154 citing papers in PubMed, 212 citations in OpenAlex.
- Trial
- Safety and activity of selinexor in patients with myelodysplastic syndromes or oligoblastic acute myeloid leukaemia refractory to hypomethylating agents: a single-centre, single-arm, phase 2 trial.The Lancet. Haematology · 2020Trial
- Serine Starvation Modulates mRNA Splicing through Translational Inhibition of SRSF Proteins.Cancer research · 2026Article
- Sensitivity to ATR-CHK1 pathway inhibition in MDS/AML is enhanced by SRSF2 mutations and reduced by RUNX1 loss.Leukemia · 2026Article
- SRSF2 P95H induces monocytic priming of human hematopoietic stem and progenitor cells.Leukemia · 2026Article
- PANoptosis in the pathogenesis of myelodysplastic syndromes.Molecular oncology · 2026Review
- Weakened macrophage antibacterial capacity in myelodysplastic syndrome.ImmunoHorizons · 2026Article
- Article
- Clonal hematopoiesis and its progression to myeloid neoplasms: insights into risk, biology, and therapeutic strategies.Haematologica · 2026Review
- TGFβ-activated kinase-1 knockdown in hematopoietic stem-progenitor cells causes PANoptosis and myelodysplastic syndrome-like disease in mice.Haematologica · 2026Article
- BRD9 depletion-mediated ALOX5 upregulation via chromatin dysregulation induces ferroptosis in SF3B1-mutant hematopoiesis.International journal of hematology · 2026Article
- Acidosis promotes exon skipping through sequestering SR-rich splicing factors in nuclear speckles.Frontiers in molecular biosciences · 2026Article
- RNA Splicing as a Therapeutic Target in Cancer.Annual review of pharmacology and toxicology · 2026Review
- Targeting splicing-derived neoantigens for precision cancer immunotherapy.Frontiers in immunology · 2026Review
- An inhibitor of UHM splicing factors exerts anti-leukemic activity by altering cell cycle progression and reducing lysosome acidification.Cellular signalling · 2025Article
- Setd2 ensures the establishment of a precise basal inflammatory state within murine hematopoietic stem/progenitor cells.Cell death & disease · 2025Article
- Splicing Factor Mutations in Chronic Myelomonocytic Leukemia: Biological Consequences and Therapeutic Implications.Current hematologic malignancy reports · 2025Review
- Distinct and convergent effects ofProceedings of the National Academy of Sciences of the United States of America · 2025Article
- SpliceDecoder: A High-Throughput Tool for Guiding the Functional Interpretation of Differential Splicing Events.bioRxiv : the preprint server for biology · 2025Article
- Colorectal cancer-associated PCBP1 mutations disrupt protein stability in a dominant negative manner.bioRxiv : the preprint server for biology · 2025Article
94 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
27 authors at 6 institutions in 2 countries.
Stanley Chun-Wei LeeHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Zuckerman 701, 408 East 69(th) Street, New York, NY 10065, USA.
Khrystyna NorthComputational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Mailstop: M1-B514, Seattle, WA 98109-1024, USA; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Eunhee KimSchool of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
Eunjung JangSchool of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
Esther ObengDivision of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sydney X LuHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Zuckerman 701, 408 East 69(th) Street, New York, NY 10065, USA.
Bo LiuHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Zuckerman 701, 408 East 69(th) Street, New York, NY 10065, USA.
Daichi InoueHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Zuckerman 701, 408 East 69(th) Street, New York, NY 10065, USA.
Akihide YoshimiHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Zuckerman 701, 408 East 69(th) Street, New York, NY 10065, USA.
Michelle KiHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Zuckerman 701, 408 East 69(th) Street, New York, NY 10065, USA.
Mirae YeoSchool of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
Xiao Jing ZhangHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Zuckerman 701, 408 East 69(th) Street, New York, NY 10065, USA.
Min Kyung KimHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Zuckerman 701, 408 East 69(th) Street, New York, NY 10065, USA.
Hana ChoHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Zuckerman 701, 408 East 69(th) Street, New York, NY 10065, USA.
Young Rock ChungHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Zuckerman 701, 408 East 69(th) Street, New York, NY 10065, USA.
Justin TaylorHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Zuckerman 701, 408 East 69(th) Street, New York, NY 10065, USA.
Benjamin H DurhamHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Zuckerman 701, 408 East 69(th) Street, New York, NY 10065, USA.
Young Joon KimHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Zuckerman 701, 408 East 69(th) Street, New York, NY 10065, USA.
Alessandro PastoreHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Zuckerman 701, 408 East 69(th) Street, New York, NY 10065, USA.
Sebastien MonetteLaboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, The Rockefeller University, New York, NY, USA.
James PalacinoH3 Biomedicine, Cambridge, MA, USA.
Michael SeilerH3 Biomedicine, Cambridge, MA, USA.
Silvia BuonamiciH3 Biomedicine, Cambridge, MA, USA.
Peter G SmithH3 Biomedicine, Cambridge, MA, USA.
Benjamin L EbertDivision of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Robert K BradleyComputational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Mailstop: M1-B514, Seattle, WA 98109-1024, USA; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Genome Sciences, University of Washington, Seattle, WA, USA. Electronic address: rbradley@fredhutch.org.
Omar Abdel-WahabHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Zuckerman 701, 408 East 69(th) Street, New York, NY 10065, USA; Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: abdelwao@mskcc.org.
Memorial Sloan Kettering Cancer Center · USUlsan National Institute of Science and Technology · KRFred Hutch Cancer Center · USBrigham and Women's Hospital · USBroad Institute · USRockefeller University · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MTumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8MTargeting SYK Kinase in AMLP50CA206963 · NCI · DANA-FARBER CANCER INST · PI STEGMAIER, KIMBERLY · 2017 to 2021
$10.6MGenetic and molecular basis for SRSF2 mutations in myelodysplasiaR01HL128239 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Omar Abdel-Wahab, Robert K Bradley · 2015 to 2026
$8.0MU2AF1 mutations in myelodysplastic syndromes: from mechanism to therapyR01DK103854 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BRADLEY, ROBERT K · 2016 to 2019
$1.5MFHCRC High-Performance Computing ClusterS10OD020069 · OD · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KOOPERBERG, CHARLES L · 2015 to 2015
$600kDefining Novel Genetic Dependencies in Spliceosome Mutant LeukemiaK99CA218896 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI LEE, STANLEY CHUN-WEI · 2017 to 2018
$297kU2AF1 mutations in myelodysplastic syndromes: from mechanism to therapyR56DK103854 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BRADLEY, ROBERT K · 2014 to 2014
$114kNCI NIH HHS K99 CA218896NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA206963NHLBI NIH HHS R01 HL128239NIDDK NIH HHS R01 DK103854NIDDK NIH HHS R56 DK103854NIH HHS S10 OD020069Worldwide Cancer Research 15-0399
Abstract
Mutations affecting RNA splicing factors are the most common genetic alterations in myelodysplastic syndrome (MDS) patients and occur in a mutually exclusive manner. The basis for the mutual exclusivity of these mutations and how they contribute to MDS is not well understood. Here we report that although different spliceosome gene mutations impart distinct effects on splicing, they are negatively selected for when co-expressed due to aberrant splicing and downregulation of regulators of hematopoietic stem cell survival and quiescence. In addition to this synthetic lethal interaction, mutations in the splicing factors SF3B1 and SRSF2 share convergent effects on aberrant splicing of mRNAs that promote nuclear factor κB signaling. These data identify shared consequences of splicing-factor mutations and the basis for their mutual exclusivity.
Indexed as
MutationSpliceosomesAnimalsCaspase 8FemaleHematopoiesisHumansMaleMiceMice, Inbred C57BLNeoplasmsNF-kappa BPhosphoproteinsRNA Splicing FactorsSerine-Arginine Splicing FactorsCaspase 8NF-kappa BPhosphoproteinsRNA Splicing FactorsSerine-Arginine Splicing FactorsSF3B1 protein, humanSRSF2 protein, humanmyelodysplastic syndromesNF-κBSF3B1splicingSRSF2U2AF1
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