Evidence map›Paper›PMID 39543396›Full record

ArticleThe EMBO journal2024

Redistribution of PU.1 partner transcription factor RUNX1 binding secures cell survival during leukemogenesis.

Alexander Bender, Füsun Boydere, Ashok Kumar Jayavelu, Alessia Tibello, Thorsten König, Hanna Aleth, Gerd Meyer Zu Hörste, Thomas Vogl, Frank Rosenbauer

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The EMBO journal, 2024. 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. Article
  2. 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

9 authors.

Alexander Bender *Institute of Molecular Tumor Biology, University of Münster, Münster, Germany.
Füsun Boydere *Institute of Molecular Tumor Biology, University of Münster, Münster, Germany.
Ashok Kumar JayaveluProteomics and Cancer Cell Signaling, Clinical Cooperation Unit Pediatric Leukemia, German Cancer Research Center (DKFZ) and Hopps Children's Cancer Center (KiTZ), University of Heidelberg, Heidelberg, Germany.
Alessia TibelloInstitute of Molecular Tumor Biology, University of Münster, Münster, Germany.
Thorsten KönigInstitute of Molecular Tumor Biology, University of Münster, Münster, Germany.
Hanna AlethInstitute of Molecular Tumor Biology, University of Münster, Münster, Germany.
Gerd Meyer Zu HörsteDepartment of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany.
Thomas VoglInstitute of Immunology, University of Münster, Münster, Germany.
Frank RosenbauerInstitute of Molecular Tumor Biology, University of Münster, Münster, Germany. frank.rosenbauer@ukmuenster.de.ORCID http://orcid.org/0000-0001-7977-9421

Funding

Deutsche Forschungsgemeinschaft (DFG) CRCTRR332 B03Deutsche Forschungsgemeinschaft (DFG) CRCTRR332 C07Interdisciplinary Center of Clinical Research Medical Faculty of the University of Münster Ros4-003-23
6 · The paper itself

Abstract

Transcription factors (TFs) orchestrating lineage-development often control genes required for cellular survival. However, it is not well understood how cells survive when such TFs are lost, for example in cancer. PU.1 is an essential TF for myeloid fate, and mice with downregulated PU.1 levels develop acute myeloid leukemia (AML). Combining a multi-omics approach with a functional genetic screen, we reveal that PU.1-downregulated cells fundamentally change their survival control from cytokine-driven pathways to overexpression of an autophagy-predominated stem cell gene program, for which we also find evidence in human AML. Control of this program involves redirected chromatin occupancy of the PU.1 partner TF Runx1 to a lineage-inappropriate binding site repertoire. Hence, genomic reallocation of TF binding upon loss of a partner TF can act as a pro-oncogenic failsafe mechanism by sustaining cell survival during leukemogenesis.

Indexed as

Cell SurvivalCore Binding Factor Alpha 2 SubunitLeukemia, Myeloid, AcuteProto-Oncogene ProteinsTrans-ActivatorsAnimalsCarcinogenesisHumansMiceProtein BindingProto-Oncogene Protein Spi-1Core Binding Factor Alpha 2 SubunitProto-Oncogene ProteinsProto-Oncogene Protein Spi-1RUNX1 protein, humanRunx1 protein, mouseTrans-ActivatorsMyeloid DevelopmentMyeloid LeukemiaPU.1RUNX1

Identifiers

PMID39543396
PMCPMC11649769

What Socratic 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 Socratic graph.