Evidence map›Paper›PMID 34162911›Full record

ArticleScientific reports2021

Focused CRISPR-Cas9 genetic screening reveals USO1 as a vulnerability in B-cell acute lymphoblastic leukemia.

Amit Kumar Jaiswal, Hellen Truong, Tiffany M Tran, Tasha L Lin, David Casero, Michael O Alberti, Dinesh S Rao

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

18 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
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  6. IGF2BP3 remodels the microRNA targeting landscape in MLL-AF4 leukemia.bioRxiv : the preprint server for biology · 2025
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. USO1 expression is dysregulated in non-small cell lung cancer.Translational lung cancer research · 2022
    Article
  16. Review
  17. Article
  18. Review
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

7 authors at 4 institutions in 1 country.

Amit Kumar JaiswalDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine At UCLA, Los Angeles, CA, 90095, USA.
Hellen TruongDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine At UCLA, Los Angeles, CA, 90095, USA.
Tiffany M TranDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine At UCLA, Los Angeles, CA, 90095, USA.
Tasha L LinDepartment of Internal Medicine, Division of Hematology/Oncology, UCLA, Los Angeles, USA.
David CaseroF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, CA, 90048, USA.
Michael O AlbertiDepartment of Pathology, Washington University, St. Louis, USA.
Dinesh S RaoDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine At UCLA, Los Angeles, CA, 90095, USA. drao@mednet.ucla.edu.
University of California, Los Angeles · USBroad Center · USCedars-Sinai Medical Center · USWashington University in St. Louis · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANTON, PETER A · 1991 to 2018
$39.9M
TUMOR CELL SURFACES AND CHROMOSOMEST32CA009056 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Gay M Crooks, David A. Nathanson · 1985 to 2026
$10.5M
UCLA Tumor Immunology Training ProgramT32CA009120 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Steven M. Dubinett, MICHAEL A TEITELL · 1985 to 2026
$10.3M
Characterizing tumor suppressive functions of microRNAs in B-cell neoplasiaR01CA166450 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RAO, DINESH S · 2013 to 2017
$2.5M
RNA-Binding Proteins in the control of B-Cell DevelopmentR21AI132869 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RAO, DINESH S · 2017 to 2018
$428k
Pathogenetic roles of USO1 in leukemogenesisR03CA251845 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RAO, DINESH S · 2021 to 2022
$156k
NCI NIH HHS P30 CA016042NCI NIH HHS R01 CA166450NCI NIH HHS R01CA166450NCI NIH HHS R03 CA251845NCI NIH HHS T32 CA009056NCI NIH HHS T32 CA009120NCI NIH HHS T32CA009120NIAID NIH HHS P30 AI028697NIAID NIH HHS R21 AI132869NIH/NIAID R21AI132869
6 · The paper itself

Abstract

Post-transcriptional gene regulation, including that by RNA binding proteins (RBPs), has recently been described as an important mechanism in cancer. We had previously identified a set of RBPs that were highly dysregulated in B-cell acute lymphoblastic leukemia (B-ALL) with MLL translocations, which carry a poor prognosis. Here, we sought to functionally characterize these dysregulated RBP genes by performing a focused CRISPR dropout screen in B-ALL cell lines, finding dependencies on several genes including EIF3E, EPRS and USO1. Validating our findings, CRISPR/Cas9-mediated disruption of USO1 in MLL-translocated B-ALL cells reduced cell growth, promoted cell death, and altered the cell cycle. Transcriptomic analysis of USO1-deficient cells revealed alterations in pathways related to mTOR signaling, RNA metabolism, and targets of MYC. In addition, USO1-regulated genes from these experimental samples were significantly and concordantly correlated with USO1 expression in primary samples collected from B-ALL patients. Lastly, we found that loss of Uso1 inhibited colony formation of MLL-transformed in primary bone marrow cells from Cas9-EGFP mice. Together, our findings demonstrate an approach to performing focused sub-genomic CRISPR screens and highlight a putative RBP vulnerability in MLL-translocated B-ALL, thus identifying potential therapeutic targets in this disease.

Indexed as

CRISPR-Cas SystemsAnimalsCell CycleCell Line, TumorCell ProliferationGene Expression Regulation, LeukemicGenes, ReporterGenetic Predisposition to DiseaseGenetic TestingGolgi Matrix ProteinsHomeostasisHumansMiceMice, Inbred C57BLMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsGolgi Matrix ProteinsMLL-AF4 fusion protein, humanMyeloid-Lymphoid Leukemia ProteinNeoplasm ProteinsOncogene Proteins, FusionRNA, Neoplasmvesicular transport factor p115Vesicular Transport Proteins

Identifiers

PMID34162911
PMCPMC8222245
OpenAlexW3176284022

What OpenQuestion holds

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Registered trials

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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.