Evidence map›Paper›PMID 22451420›Full record

ArticleBlood2012

Runx1 deletion or dominant inhibition reduces Cebpa transcription via conserved promoter and distal enhancer sites to favor monopoiesis over granulopoiesis.

Hong Guo, Ou Ma, Nancy A Speck, Alan D Friedman

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

64 citing papers in PubMed, 97 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. C/EBPα activatesScience immunology · 2025
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  8. Article
  9. Comprehensive summary: the role of PBX1 in development and cancers.Frontiers in cell and developmental biology · 2024
    Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

4 more citing papers are in PubMed but not listed here.

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

4 authors at 2 institutions in 1 country.

Hong GuoDivision of Pediatric Oncology, Johns Hopkins University, Baltimore, MD 21231, USA.
Ou Ma
Nancy A Speck
Alan D Friedman
Johns Hopkins University · USUniversity of Pennsylvania · US

Funding

Basic and Translational Research of iPSC-Based hematologic and Vascular TherapiesU01HL099775 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI FRIEDMAN, ALAN D · 2009 to 2015
$8.4M
Expansion of cardiac and hematopoietic progenitors by Wnt and NotchU01HL100405 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI EPSTEIN, JONATHAN A., MORRISEY, EDWARD E · 2009 to 2015
$8.1M
Basic and Translational Research iPSC-based hematologic and vascular therapiesU01HL100397 · NHLBI · STANFORD UNIVERSITY · PI COOKE, JOHN P · 2009 to 2015
$7.4M
BIOCHEMISTRY OF LEUKEMIA VIRUS CORE-BINDING FACTORR01CA058343 · NCI · DARTMOUTH COLLEGE · PI SPECK, NANCY ASMUSSEN · 1993 to 2007
$3.0M
Regulation of Monocyte and Granulocyte Lineage SpecificationR01HL089176 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI FRIEDMAN, ALAN D · 2009 to 2013
$2.0M
NCI NIH HHS R01 CA058343NHLBI NIH HHS R01 HL089176NHLBI NIH HHS U01 HL099775NHLBI NIH HHS U01 HL099775/HL100397NHLBI NIH HHS U01 HL100397NHLBI NIH HHS U01 HL100405
6 · The paper itself

Abstract

Deletion of Runx1 in adult mice produces a myeloproliferative phenotype. We now find that Runx1 gene deletion increases marrow monocyte while reducing granulocyte progenitors and that exogenous RUNX1 rescues granulopoiesis. Deletion of Runx1 reduces Cebpa mRNA in lineage-negative marrow cells and in granulocyte-monocyte progenitors or common myeloid progenitors. Pu.1 mRNA is also decreased, but to a lesser extent. We also transduced marrow with dominant-inhibitory RUNX1a. As with Runx1 gene deletion, RUNX1a expands lineage-Sca-1+c-kit+ and myeloid cells, increased monocyte CFUs relative to granulocyte CFUs, and reduced Cebpa mRNA. Runx1 binds a conserved site in the Cebpa promoter and binds 4 sites in a conserved 450-bp region located at +37 kb; mutation of the enhancer sites reduces activity 6-fold in 32Dcl3 myeloid cells. Endogenous Runx1 binds the promoter and putative +37 kb enhancer as assessed by ChIP, and RUNX1-ER rapidly induces Cebpa mRNA in these cells, even in cycloheximide, consistent with direct gene regulation. The +37 kb region contains strong H3K4me1 histone modification and p300-binding, as often seen with enhancers. Finally, exogenous C/EBPα increases granulocyte relative to monocyte progenitors in Runx1-deleted marrow cells. Diminished CEBPA transcription and consequent impairment of myeloid differentiation may contribute to leukemic transformation in acute myeloid leukemia cases associated with decreased RUNX1 activity.

Indexed as

AnimalsBinding SitesCCAAT-Enhancer-Binding ProteinsCells, CulturedCore Binding Factor Alpha 2 SubunitDown-RegulationEnhancer Elements, GeneticGene DeletionGenes, DominantGranulocytesHEK293 CellsHematopoiesisHumansLeukemia, Myeloid, AcuteMiceMice, Inbred C57BLCCAAT-Enhancer-Binding ProteinsCEBPA protein, mouseCore Binding Factor Alpha 2 SubunitRunx1 protein, mouse

Identifiers

PMID22451420
PMCPMC3362359
OpenAlexW2025187528

What OpenQuestion holds

Textmetadata
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.