Evidence map›Paper›PMID 34546980›Full record

ArticleThe Journal of clinical investigation2021

U2af1 is a haplo-essential gene required for hematopoietic cancer cell survival in mice.

Brian A Wadugu, Sridhar Nonavinkere Srivatsan, Amanda Heard, Michael O Alberti, Matthew Ndonwi, Jie Liu, Sarah Grieb, Joseph Bradley, Jin Shao, Tanzir Ahmed and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.2field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. U2af1Leukemia · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. bioRxiv : the preprint server for biology · 2024
    Article
  7. Article
  8. Article
  9. Article
  10. Impact of genome build on RNA-seq interpretation and diagnostics.medRxiv : the preprint server for health sciences · 2024
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 1 country.

Brian A WaduguDivision of Oncology, Department of Medicine and.
Sridhar Nonavinkere SrivatsanDivision of Oncology, Department of Medicine and.
Amanda HeardDivision of Oncology, Department of Medicine and.
Michael O AlbertiDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Matthew NdonwiDivision of Oncology, Department of Medicine and.
Jie LiuDivision of Oncology, Department of Medicine and.
Sarah GriebDivision of Oncology, Department of Medicine and.
Joseph BradleyDivision of Oncology, Department of Medicine and.
Jin ShaoDivision of Oncology, Department of Medicine and.
Tanzir AhmedDivision of Oncology, Department of Medicine and.
Cara L ShiraiDivision of Oncology, Department of Medicine and.
Ajay KhannaDivision of Oncology, Department of Medicine and.
Dennis L FeiDepartment of Medicine, Meyer Cancer Center, Weill Cornell Medicine, New York, New York, USA.
Christopher A MillerDivision of Oncology, Department of Medicine and.
Timothy A GraubertMassachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts, USA.
Matthew J WalterDivision of Oncology, Department of Medicine and.
Cornell University · USHarvard University · USWashington University in St. Louis · US

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI AIMEE S JAMES · 2001 to 2026
$128.0M
Specimen Acquistition and Expression ProfilingP01CA101937 · NCI · WASHINGTON UNIVERSITY · PI LINK, DANIEL C · 2003 to 2023
$58.8M
Targeting the Bone Marrow Microenvironment In Acute Lymphocytic LeukemiaP50CA171963 · NCI · WASHINGTON UNIVERSITY · PI Daniel C Link · 2013 to 2026
$31.6M
Washington University Paul Calabresi K12 Career Development Award for Clinical OncologyK12CA167540 · NCI · WASHINGTON UNIVERSITY · PI John F. Dipersio, Ramaswamy Govindan · 2012 to 2026
$11.7M
COMPREHENSIVE INFORMATIC ANALYSES OF AML GENOMES AND EPIGENOMESR50CA211782 · NCI · WASHINGTON UNIVERSITY · PI Christopher A Miller · 2017 to 2026
$1.5M
NCI NIH HHS K12 CA167540NCI NIH HHS P01 CA101937NCI NIH HHS P30 CA091842NCI NIH HHS P50 CA171963NCI NIH HHS R50 CA211782
6 · The paper itself

Abstract

Somatic mutations in the spliceosome gene U2AF1 are common in patients with myelodysplastic syndromes. U2AF1 mutations that code for the most common amino acid substitutions are always heterozygous, and the retained WT allele is expressed, suggesting that mutant hematopoietic cells may require the residual WT allele to be viable. We show that hematopoiesis and RNA splicing in U2af1 heterozygous knockout mice were similar to those in control mice, but that deletion of the WT allele in U2AF1(S34F) heterozygous mutant-expressing hematopoietic cells (i.e., hemizygous mutant) was lethal. These results confirm that U2AF1 mutant hematopoietic cells are dependent on the expression of WT U2AF1 for survival in vivo and that U2AF1 is a haplo-essential cancer gene. Mutant U2AF1(S34F)-expressing cells were also more sensitive to reduced expression of WT U2AF1 than nonmutant cells. Furthermore, mice transplanted with leukemia cells expressing mutant U2AF1 had significantly reduced tumor burden and improved survival after the WT U2af1 allele was deleted compared with when it was not deleted. These results suggest that selectively targeting the WT U2AF1 allele in heterozygous mutant cells could induce cancer cell death and be a therapeutic strategy for patients harboring U2AF1 mutations.

Indexed as

AllelesHematologic NeoplasmsHeterozygoteLeukemiaNeoplasm ProteinsNeoplasms, ExperimentalSplicing Factor U2AFAnimalsMiceMice, KnockoutNeoplasm ProteinsSplicing Factor U2AFZrsr1 protein, mouseCancerHematologyLeukemiasOncologyRNA processing

Identifiers

PMID34546980
PMCPMC8553566
OpenAlexW3199683944

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.