ArticleCancer cell2015
SRSF2 Mutations Contribute to Myelodysplasia by Mutant-Specific Effects on Exon Recognition.
Registry-linked trialOpen access · bronzeAbstract read
In one paragraph
Article in Cancer cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03907553 (Aging of Hematopoietic Stem Cells - Molecular Architecture of Marrow Dysplasia and Clinical Contribution of Ineffective Hematopoiesis to Frailty in the Elderly), which is not on this map. Cited by 418 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
418citing papers in PubMed, 1 pooled it
34.3field-weighted citation impact, top 1% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Aging of Hematopoietic Stem Cells - Molecular Architecture of Marrow Dysplasia and Clinical Contribution of Ineffective Hematopoiesis to Frailty in the Elderly
Who cites it
418 citing papers in PubMed, 1 synthesis or guideline pooled it, 562 citations in OpenAlex.
- The Coming of Age of Preclinical Models of MDS.Frontiers in oncology · 2022Pooled it
- A phase 1b/2 study of ceralasertib, a selective inhibitor of ATR, in patients with relapsed or refractory MDS and CMML.Blood advances · 2026Trial
- Spliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia.Annals of hematology · 2023Trial
- ZC3H14 phosphorylation is required for nuclear speckle assembly during zygotic splicing activation in mice.EMBO reports · 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
- An antisense antidote to oncogenic poison exons.Genes & development · 2026Article
- TargetingGenes & development · 2026Article
- Single-cell long-read genotyping of transcripts reveals discrete mechanisms of clonal evolution in post-MPN AML.Blood advances · 2026Article
- PANoptosis in the pathogenesis of myelodysplastic syndromes.Molecular oncology · 2026Review
- Nonsense-Mediated RNA Decay Is a Targetable Vulnerability in Splicing Factor Mutant Myeloid Neoplasms by Enhancing R-Loop Accumulation and DNA Damage.Cancer research · 2026Article
- Splicing-driven post-translational dysregulation: a new frontier for precision cancer medicine and immunotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Article
- Inflammatory Signatures in MDS: The Missing Link Between Genetics, Microenvironment, and Therapy.Cells · 2026Review
- Review
- Alternative splicing rewires breast cancer and opens therapeutic avenues.Cell communication and signaling : CCS · 2026Review
- Long-read cDNA sequencing reveals novel isoforms and spliceosome-mutant-enriched transcripts in AML and MDS.bioRxiv : the preprint server for biology · 2026Article
- A U1-U3 snRNA-snoRNA interaction couples SF3B1 mutation to chromatin-state rewiring and genome instability.bioRxiv : the preprint server for biology · 2026Article
- Nonsense-mediated mRNA decay: friend or foe in cancer biology?Cell communication and signaling : CCS · 2026Review
- Role of alternative splicing in cancer progression.Irish journal of medical science · 2026Review
358 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
25 authors at 9 institutions in 4 countries.
Eunhee KimHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Janine O IlaganComputational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Yang LiangHematology, Yale Comprehensive Cancer Center and Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Gerrit M DaubnerInstitute for Molecular Biology and Biophysics, ETH, 8093 Zürich, Switzerland.
Stanley C-W LeeHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Aravind RamakrishnanClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Division of Medical Oncology, School of Medicine, University of Washington, Seattle, WA 98109, USA.
Yue LiDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Young Rock ChungHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jean-Baptiste MicolHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Michele E MurphyClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Hana ChoHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Min-Kyung KimHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Ahmad S ZebariComputational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Shlomzion AumannHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Christopher Y ParkHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Silvia BuonamiciH3 Biomedicine, Cambridge, MA 03129, USA.
Peter G SmithH3 Biomedicine, Cambridge, MA 03129, USA.
H Joachim DeegClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Division of Medical Oncology, School of Medicine, University of Washington, Seattle, WA 98109, USA.
Camille LobryInstitut National de la Santé et de la Recherche Medicale (INSERM) U1009, Institut Gustave Roussy, 94805 Villejuif, France; Université Paris-Sud, 91400 Orsay, France.
Iannis AifantisHoward Hughes Medical Institute and Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Yorgo ModisDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA; Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Frederic H-T AllainInstitute for Molecular Biology and Biophysics, ETH, 8093 Zürich, Switzerland.
Stephanie HaleneHematology, Yale Comprehensive Cancer Center and Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Robert K BradleyComputational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: rbradley@fhcrc.org.
Omar Abdel-WahabHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: abdelwao@mskcc.org.
Memorial Sloan Kettering Cancer Center · USFred Hutch Cancer Center · USUniversity of Washington Medical Center · USYale Cancer Center · USCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZAHoward Hughes Medical Institute · USMRC Laboratory of Molecular Biology · GBUniversité Paris-Sud · FRYale University · US
Funding
Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4MYale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI MEGAN C KING · 1985 to 2026
$85.0MCORE--VECTOR PRODUCTIONP30DK056465 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BERNSTEIN, IRWIN D · 1999 to 2014
$14.9MControlling Hematopoietic Lineage Commitment from ESC to PlateletsU01HL099993 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI TOROK-STORB, BEVERLY J. · 2009 to 2015
$8.3MChromosome Metabolism and Cancer Training GrantT32CA009657 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI EISENMAN, ROBERT NEIL · 1991 to 2020
$7.6MSummer research experiences for medical students supervised by faculty mentorsR25CA020449 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Charlotte Eielson Ariyan · 1985 to 2026
$6.2MGenetic Dissection of Acute Myeloid Leukemia.R01CA169784 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI AIFANTIS, IANNIS, LEVINE, ROSS L · 2014 to 2018
$1.8MThe structural basis of nucleic acid recognition by Toll-like receptorsR01GM102869 · NIGMS · YALE UNIVERSITY · PI MODIS, YORGO · 2012 to 2015
$1.1MRole of ASXL1 mutations in myeloid malignanciesK08CA160647 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ABDEL-WAHAB, OMAR · 2011 to 2015
$849kGenerating iPS cells by reprogramming using small moleculesK08DK082783 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI RAMAKRISHNAN, ARAVIND · 2009 to 2013
$671kU2AF1 mutations in myelodysplastic syndromes: from mechanism to therapyR56DK103854 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BRADLEY, ROBERT K · 2014 to 2014
$114kNCI NIH HHS 1K08CA160647-01NCI NIH HHS K08 CA160647NCI NIH HHS P30 CA015704NCI NIH HHS P30 CA016359NCI NIH HHS R01 CA169784NCI NIH HHS R25 CA020449NCI NIH HHS T32 CA009657NHLBI NIH HHS U01 HL099993NIDDK NIH HHS K08 DK082783NIDDK NIH HHS P30 DK056465NIDDK NIH HHS R56 DK103854NIGMS NIH HHS R01 GM102869Wellcome Trust 101908Wellcome Trust 101908/Z/13/ZWorldwide Cancer Research 15-0399
Abstract
Mutations affecting spliceosomal proteins are the most common mutations in patients with myelodysplastic syndromes (MDS), but their role in MDS pathogenesis has not been delineated. Here we report that mutations affecting the splicing factor SRSF2 directly impair hematopoietic differentiation in vivo, which is not due to SRSF2 loss of function. By contrast, SRSF2 mutations alter SRSF2's normal sequence-specific RNA binding activity, thereby altering the recognition of specific exonic splicing enhancer motifs to drive recurrent mis-splicing of key hematopoietic regulators. This includes SRSF2 mutation-dependent splicing of EZH2, which triggers nonsense-mediated decay, which, in turn, results in impaired hematopoietic differentiation. These data provide a mechanistic link between a mutant spliceosomal protein, alterations in the splicing of key regulators, and impaired hematopoiesis.
Indexed as
ExonsMutationAnimalsEnhancer of Zeste Homolog 2 ProteinGene ExpressionMiceMice, Mutant StrainsMyelodysplastic SyndromesNuclear ProteinsPolycomb Repressive Complex 2ProteolysisRibonucleoproteinsRNA SplicingSerine-Arginine Splicing FactorsEnhancer of Zeste Homolog 2 ProteinEzh2 protein, mouseNuclear ProteinsPolycomb Repressive Complex 2RibonucleoproteinsSerine-Arginine Splicing FactorsSRSF2 protein, mouse
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Registered trials
NCT03907553ClinicalTrials.gov
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.