Evidence map›Paper›PMID 36111891›Full record

ArticleBlood advances2023

Genome-wide CRISPR/Cas9 screen identifies etoposide response modulators associated with clinical outcomes in pediatric AML.

Nam H K Nguyen, Roya Rafiee, Abderrahmane Tagmount, Amin Sobh, Alex Loguinov, Angelica K de Jesus Sosa, Abdelrahman H Elsayed, Mohammed Gbadamosi, Nathan Seligson, Christopher R Cogle and 7 more

Open access · goldAbstract read
In one paragraph

Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.4field-weighted citation impact, top 9% 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

5 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
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  4. Review
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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

17 authors at 4 institutions in 1 country.

Nam H K NguyenDepartment of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, FL.ORCID 0000-0003-3036-4748
Roya RafieeDepartment of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, FL.
Abderrahmane TagmountDepartment of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL.ORCID 0000-0002-5415-8618
Amin SobhUF Health Cancer Center, Gainesville, FL.ORCID 0000-0003-3635-8138
Alex LoguinovDepartment of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL.
Angelica K de Jesus SosaDepartment of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, FL.ORCID 0000-0003-1463-543X
Abdelrahman H ElsayedDepartment of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, FL.
Mohammed GbadamosiDepartment of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, FL.
Nathan SeligsonDepartment of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Jacksonville, FL.ORCID 0000-0002-9670-3792
Christopher R CogleDivision of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, FL.ORCID 0000-0001-5422-6863
Jeffery RubnitzDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN.ORCID 0000-0001-9885-3527
Raul RibeiroDepartment of Oncology, St. Jude Children's Research Hospital, Memphis, TN.ORCID 0000-0002-9956-5647
James DowningDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, TN.
Xueyuan CaoUniversity of Tennessee Health Science Center, Memphis, TN.
Stanley B PoundsDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN.
Christopher D VulpeUF Health Cancer Center, Gainesville, FL.
Jatinder K LambaDepartment of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, FL.ORCID 0000-0003-0411-0007
University of Florida · USSt. Jude Children's Research Hospital · USUniversity of Florida Health · USUniversity of Tennessee Health Science Center · US

Funding

Pharmacogenomics of Ara-C in AMLR01CA132946 · NCI · UNIVERSITY OF MINNESOTA · PI LAMBA, JATINDER K., POUNDS, STANLEY BARRETT · 2008 to 2025
$5.3M
Training Program for Applied Research and Development in Genomic MedicineT32HG008958 · NHGRI · UNIVERSITY OF FLORIDA · PI Larisa Humma Cavallari, Stephen E. Kimmel · 2018 to 2026
$3.8M
NCI NIH HHS R01 CA132946NHGRI NIH HHS T32 HG008958
6 · The paper itself

Abstract

Etoposide is used to treat a wide range of malignant cancers, including acute myeloid leukemia (AML) in children. Despite the use of intensive chemotherapeutic regimens containing etoposide, a significant proportion of pediatric patients with AML become resistant to treatment and relapse, leading to poor survival. This poses a pressing clinical challenge to identify mechanisms underlying drug resistance to enable effective pharmacologic targeting. We performed a genome-wide CRISPR/Cas9 synthetic-lethal screening to identify functional modulators of etoposide response in leukemic cell line and integrated results from CRISPR-screen with gene expression and clinical outcomes in pediatric patients with AML treated with etoposide-containing regimen. Our results confirmed the involvement of well-characterized genes, including TOP2A and ABCC1, as well as identified novel genes such as RAD54L2, PRKDC, and ZNF451 that have potential to be novel drug targets. This study demonstrates the ability for leveraging CRISPR/Cas9 screening in conjunction with clinically relevant endpoints to make meaningful discoveries for the identification of prognostic biomarkers and novel therapeutic targets to overcome treatment resistance.

Indexed as

CRISPR-Cas SystemsLeukemia, Myeloid, AcuteCell LineChildDNA HelicasesEtoposideHumansDNA HelicasesEtoposideRAD54L2 protein, human

Identifiers

PMID36111891
PMCPMC10182178
OpenAlexW4296036930

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.