Evidence map›Paper›PMID 39841016›Full record

ArticleBlood2025

FLT3 is genetically essential for ITD-mutated leukemic stem cells but dispensable for human hematopoietic stem cells.

Joana L Araújo, Elvin Wagenblast, Veronique Voisin, Jessica McLeod, Olga I Gan, Suraj Bansal, Liqing Jin, Amanda Mitchell, Blaise Gratton, Sarah Cutting and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Blood, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
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  5. Review
  6. Review
  7. 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

22 authors.

Joana L AraújoPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Elvin WagenblastPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0002-0709-2759
Veronique VoisinPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Jessica McLeodPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Olga I GanPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Suraj BansalPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0003-4023-6635
Liqing JinPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Amanda MitchellPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Blaise GrattonPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Sarah CuttingPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Andrea ArrudaDepartment of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Monica DoedensPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Anthea TravasDepartment of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0009-0001-7662-7091
Dennis KimDepartment of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Jose-Mario Capo-ChichiDepartment of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0002-7440-3633
Sagi AbelsonOntario Institute for Cancer Research, Toronto, ON, Canada.ORCID 0000-0003-1747-3819
Mark D MindenDepartment of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0002-9089-8816
Jean C Y WangPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0001-7543-3917
Manuel A Sobrinho-SimõesDepartment of Hematology, Centro Hospitalar Universitário de São João, Porto, Portugal.ORCID 0000-0002-2854-8460
Perpétua Pinto-do-ÓInstituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.ORCID 0000-0002-6477-6030
Eric LechmanPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
John E DickPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0002-9527-8317

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

abstractLeukemic stem cells (LSCs) fuel acute myeloid leukemia (AML) growth and relapse, but therapies tailored toward eradicating LSCs without harming normal hematopoietic stem cells (HSCs) are lacking. FMS-like tyrosine kinase 3 (FLT3) is considered an important therapeutic target due to frequent mutation in AML and association with relapse. However, there has been limited clinical success with FLT3 drug targeting, suggesting either that FLT3 is not a vulnerability in LSC or that more potent inhibition is required, a scenario where HSC toxicity could become limiting. We tested these possibilities by ablating FLT3 using CRISPR/Cas9-mediated FLT3 knockout (FLT3-KO) in human LSCs and HSCs followed by functional xenograft assays. FLT3-KO in LSCs from FLT3-internal tandem duplication (ITD)-mutated but not FLT3-wild-type AMLs resulted in short-term leukemic grafts of FLT3-KO edited cells that disappeared by 12 weeks. By contrast, FLT3-KO in HSCs from the fetal liver, cord blood, and adult bone marrow did not impair multilineage hematopoiesis in primary and secondary xenografts. Our study establishes FLT3 as an ideal therapeutic target where ITD-positive LSCs are eradicated upon FLT3 deletion whereas HSCs are spared. These findings support the development of more potent FLT3-targeting drugs or gene-editing approaches for LSC eradication to improve clinical outcomes.

Indexed as

fms-Like Tyrosine Kinase 3Hematopoietic Stem CellsLeukemia, Myeloid, AcuteMutationNeoplastic Stem CellsTandem Repeat SequencesAnimalsCRISPR-Cas SystemsHumansMiceFLT3 protein, humanfms-Like Tyrosine Kinase 3

Identifiers

PMID39841016
PMCPMC12824609

What Socratic 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 Socratic graph.