Evidence map›Paper›PMID 33076970›Full record

ArticleJournal of hematology & oncology2020

Synergistic effect of BCL2 and FLT3 co-inhibition in acute myeloid leukemia.

Lindsey T Brinton, Pu Zhang, Katie Williams, Daniel Canfield, Shelley Orwick, Steven Sher, Ronni Wasmuth, Larry Beaver, Casey Cempre, Jordan Skinner and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hematology & oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
5.3field-weighted citation impact, top 3% 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

40 citing papers in PubMed, 61 citations in OpenAlex.

  1. Azacitidine, Venetoclax, and Gilteritinib in Newly Diagnosed and Relapsed or RefractoryJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024
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  13. Mitoxantrone-liposome SensitizesJournal of Cancer · 2025
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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 3 institutions in 1 country.

Lindsey T BrintonDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Pu ZhangDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Katie WilliamsDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Daniel CanfieldDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Shelley OrwickDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Steven SherDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Ronni WasmuthDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Larry BeaverDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Casey CempreDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Jordan SkinnerDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Matthew CannonDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Mukul GovandeDepartment of Biomedical Engineering, The Ohio State University, Room 455C, OSUCCC Building, 410 West 12th Avenue, Columbus, OH, 43210, USA.
Bonnie HarringtonCollege of Veterinary Medicine, Michigan State University, Lansing, MI, USA.
Amy LehmanCenter Biostatistics, The Ohio State University, Columbus, OH, USA.
John C ByrdDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
Rosa LapalombellaDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA. rosa.lapalombella@osumc.edu.
James S BlachlyDivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
The Ohio State University · USThe Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · USMichigan State University · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3M
Targeted Therapy for LeukemiaR35CA197734 · NCI · UNIVERSITY OF CINCINNATI · PI BYRD, JOHN C. · 2015 to 2021
$6.6M
Targeting NAMPT in Acute Myeloid LeukemiaR01CA223165 · NCI · OHIO STATE UNIVERSITY · PI LAPALOMBELLA, ROSA, MIMS, ALICE SCOTT · 2018 to 2022
$2.3M
NCI NIH HHS P30 CA016058NCI NIH HHS R01 CA223165NCI NIH HHS R35 CA197734
6 · The paper itself

Abstract

Acute myeloid leukemia (AML) is a heterogeneous and complex disease, and treatments for this disease have not been curative for the majority of patients. In younger patients, internal tandem duplication of FLT3 (FLT3-ITD) is a common mutation for which two inhibitors (midostaurin and gilteritinib) with varied potency and specificity for FLT3 are clinically approved. However, the high rate of relapse or failed initial response of AML patients suggests that the addition of a second targeted therapy may be necessary to improve efficacy. Using an unbiased large-scale CRISPR screen, we genetically identified BCL2 knockout as having synergistic effects with an approved FLT3 inhibitor. Here, we provide supportive studies that validate the therapeutic potential of the combination of FLT3 inhibitors with venetoclax in vitro and in vivo against multiple models of FLT3-ITD-driven AML. Our unbiased approach provides genetic validation for co-targeting FLT3 and BCL2 and repurposes CRISPR screening data, utilizing the genome-wide scope toward mechanistic understanding.

Indexed as

Aniline CompoundsAnimalsAntineoplastic AgentsBridged Bicyclo Compounds, HeterocyclicCell Line, TumorCRISPR-Cas SystemsFemalefms-Like Tyrosine Kinase 3Gene Knockout TechniquesGenetic TherapyHumansLeukemia, Myeloid, AcuteMice, SCIDProtein Kinase InhibitorsProto-Oncogene Proteins c-bcl-2PyrazinesAniline CompoundsAntineoplastic AgentsBridged Bicyclo Compounds, HeterocyclicFLT3 protein, humanfms-Like Tyrosine Kinase 3gilteritinibmidostaurinProtein Kinase InhibitorsProto-Oncogene Proteins c-bcl-2PyrazinesStaurosporineSulfonamidesvenetoclaxAcute myeloid leukemiaBCL2Combination therapyFLT3GilteritinibMidostaurinSynergyVenetoclax

Identifiers

PMID33076970
PMCPMC7574303
OpenAlexW3093272229

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.