ArticleThe Journal of clinical investigation2021
U2af1 is a haplo-essential gene required for hematopoietic cancer cell survival in mice.
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.
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Who cites it
17 citing papers in PubMed, 18 citations in OpenAlex.
- U2AF1 mutations rescue deleterious exon skipping induced by KRAS mutations.Nature genetics · 2026Article
- U2af1Leukemia · 2026Article
- U2AF1 mutations rescue deleterious exon skipping induced by KRAS mutations.bioRxiv : the preprint server for biology · 2025Article
- Acute Myeloid Leukemia Genome Characterization Study and Subtype Classification Employing Feature Selection and Bayesian Networks.Biomedicines · 2025Article
- Article
- Article
- Impact of genome build on RNA-seq interpretation and diagnostics.American journal of human genetics · 2024Article
- Comprehensive Analyses of the Effects of the Small-Molecule Inhibitor of the UHM Domain in the Splicing FactorResearch square · 2024Article
- Single-tube Ptprc SNP genotyping of JAXBoy (CD45.1) and C57BL/6J (CD45.2) mice by endpoint PCR and gel electrophoresis.Molecular and cellular probes · 2024Article
- Impact of genome build on RNA-seq interpretation and diagnostics.medRxiv : the preprint server for health sciences · 2024Article
- Histidine N1-position-specific methyltransferase CARNMT1 targets C3H zinc finger proteins and modulates RNA metabolism.Genes & development · 2023Article
- Profiling the Binding Activities of Peptides and Inhibitors to the U2 Auxiliary Factor Homology Motif (UHM) Domains.ACS medicinal chemistry letters · 2023Article
- Splicing factor deficits render hematopoietic stem and progenitor cells sensitive to STAT3 inhibition.Cell reports · 2022Article
- The Biological and Clinical Consequences of RNA Splicing Factor U2AF1 Mutation in Myeloid Malignancies.Cancers · 2022Review
- Recurrent Spliceosome Mutations in Cancer: Mechanisms and Consequences of Aberrant Splice Site Selection.Cancers · 2022Review
- Review
- Aberrant Alternative Splicing in U2af1/Tet2 Double Mutant Mice Contributes to Major Hematological Phenotypes.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
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.
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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.