Evidence map›Paper›PMID 40763310›Full record

ArticleThe Journal of clinical investigation2025

CBFβ-SMMHC-driven leukemogenesis requires enhanced RUNX1-DNA binding affinity in mice.

Tao Zhen, Yaqiang Cao, Tongyi Dou, Yun Chen, Guadalupe Lopez, Ana Catarina Menezes, Xufeng Wu, John A Hammer, Jun Cheng, Lisa Garrett and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

21 authors.

Tao ZhenOncogenesis and Development Section, Translational and Functional Genomics Branch, National Human Genome Research Institute (NHGRI), NIH, Bethesda, Maryland, USA.
Yaqiang CaoLaboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.
Tongyi DouLaboratory of Membrane Proteins and Structural Biology, NHLBI, NIH, Bethesda, Maryland, USA.
Yun ChenMechanism of DNA Repair, Replication, and Recombination Section, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA.
Guadalupe LopezOncogenesis and Development Section, Translational and Functional Genomics Branch, National Human Genome Research Institute (NHGRI), NIH, Bethesda, Maryland, USA.
Ana Catarina MenezesOncogenesis and Development Section, Translational and Functional Genomics Branch, National Human Genome Research Institute (NHGRI), NIH, Bethesda, Maryland, USA.
Xufeng WuCell and Developmental Biology Center, NHLBI, NIH, Bethesda, Maryland, USA.
John A HammerCell and Developmental Biology Center, NHLBI, NIH, Bethesda, Maryland, USA.
Jun ChengTransgenic Mouse Core.
Lisa GarrettTransgenic Mouse Core.
Stacie AndersonFlow Cytometry Core.
Martha KirbyFlow Cytometry Core.
Stephen WincovitchAdvanced Imaging and Analysis Core, and.
Bayu SisayMicroarrays and Single-Cell Genomics Core, NHGRI, NIH, Bethesda, Maryland, USA.
Abdel G ElkahlounMicroarrays and Single-Cell Genomics Core, NHGRI, NIH, Bethesda, Maryland, USA.
Di WuBiophysics Core, NHLBI, NIH, Bethesda, Maryland, USA.
Lucio H CastillaDepartment of Molecular, Cell and Cancer Biology, Chan Medical School, University of Massachusetts, Worcester, Massachusetts, USA.
Wei YangMechanism of DNA Repair, Replication, and Recombination Section, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA.
Jiansen JiangLaboratory of Membrane Proteins and Structural Biology, NHLBI, NIH, Bethesda, Maryland, USA.
Keji ZhaoLaboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, USA.
P Paul LiuOncogenesis and Development Section, Translational and Functional Genomics Branch, National Human Genome Research Institute (NHGRI), NIH, Bethesda, Maryland, USA.

Funding

MOLECULAR PATHOGENESIS OF CHROMOSOME 16 INVERSION INHUMAN LEUKEMIAZIAHG000030 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI LIU, PAUL · 2009 to 2025
$15.8M
Intramural NIH HHS ZIA HG000030
6 · The paper itself

Abstract

The leukemia fusion gene CBFB-MYH11 requires RUNX1 for leukemogenesis, but the underlying mechanism is unclear. By in vitro studies, we found that CBFβ-SMMHC, the chimeric protein encoded by CBFB-MYH11, could enhance the binding affinity between RUNX1 and its target DNA. Increased RUNX1-DNA binding was also observed in myeloid progenitor cells from mice expressing CBFβ-SMMHC. Moreover, only CBFβ-SMMHC variants able to enhance the DNA binding affinity by RUNX1 could induce leukemia in mouse models. Marked transcriptomic changes, affecting genes associated with inflammatory response and target genes of CBFA2T3, were observed in mice expressing leukemogenic CBFβ-SMMHC variants. Finally, we show that CBFβ-SMMHC could not induce leukemia in mice with a Runx1-R188Q mutation, which reduces RUNX1 DNA binding but does not affect its interaction with CBFβ-SMMHC or its sequestration to cytoplasm by CBFβ-SMMHC. Our data suggest that, in addition to binding RUNX1 to regulate gene expression, enhancing RUNX1 binding affinity to its target DNA is an important mechanism by which CBFβ-SMMHC contributes to leukemogenesis, highlighting RUNX1-DNA interaction as a potential therapeutic target in inv(16) acute myeloid leukemia.

Indexed as

Core Binding Factor Alpha 2 SubunitCore Binding Factor beta SubunitMyosin Heavy ChainsOncogene Proteins, FusionAnimalsGene Expression Regulation, LeukemicHumansMiceMice, TransgenicMutation, MissenseCBFbeta-MYH11 fusion proteinCbfb protein, mouseCore Binding Factor Alpha 2 SubunitCore Binding Factor beta SubunitMyosin Heavy ChainsOncogene Proteins, FusionRunx1 protein, mouseGeneticsHematologyLeukemiasMouse modelsTranscriptomics

Identifiers

PMID40763310
PMCPMC12483565

What OpenQuestion holds

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LicenceCC BY
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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.