Evidence map›Paper›PMID 20876458›Full record

ArticleBlood2010

Regulation of platelet myosin light chain (MYL9) by RUNX1: implications for thrombocytopenia and platelet dysfunction in RUNX1 haplodeficiency.

Gauthami Jalagadugula, Guangfen Mao, Gurpreet Kaur, Lawrence E Goldfinger, Danny N Dhanasekaran, A Koneti Rao

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 9% 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

43 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Transcription factor RUNX1 regulates coagulation factor XIII-A (Research and practice in thrombosis and haemostasis · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Bleeding risks for uncharacterized platelet function disorders.Research and practice in thrombosis and haemostasis · 2020
    Article
  17. Article
  18. Article
  19. New Insights Into the Differentiation of Megakaryocytes From Hematopoietic Progenitors.Arteriosclerosis, thrombosis, and vascular biology · 2019
    Review
  20. 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

6 authors at 2 institutions in 3 countries.

Gauthami JalagadugulaSol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Guangfen Mao
Gurpreet Kaur
Lawrence E Goldfinger
Danny N Dhanasekaran
A Koneti Rao
Thrombosis Research Institute · GBTemple University · US

Funding

Training in Thrombosis, Hemostasis and Vascular BiologyT32HL007777 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KUNAPULI, SATYA P. · 1993 to 2012
$5.2M
SIGNAL TRANSDUCTION DEFECTS IN HUMAN PLATELETSR01HL056724 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI RAO, ANGARA KONETI · 1998 to 2006
$1.9M
R-Ras signaling in vascular biologyR01HL093416 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI GOLDFINGER, LAWRENCE E · 2010 to 2014
$1.9M
Aberrant Platelet Mechanisms in Inherited Human Platelet Function DisordersR01HL085422 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI RAO, ANGARA KONETI · 2007 to 2010
$1.5M
NHLBI NIH HHS HL007777NHLBI NIH HHS HL093416NHLBI NIH HHS R01 HL056724NHLBI NIH HHS R01 HL085422NHLBI NIH HHS R01 HL093416NHLBI NIH HHS R01HL56724NHLBI NIH HHS R01HL85422NHLBI NIH HHS T32 HL007777
6 · The paper itself

Abstract

Mutations in transcription factor RUNX1 are associated with familial platelet disorder, thrombocytopenia, and predisposition to leukemia. We have described a patient with thrombocytopenia and impaired agonist-induced platelet aggregation, secretion, and glycoprotein (GP) IIb-IIIa activation, associated with a RUNX1 mutation. Platelet myosin light chain (MLC) phosphorylation and transcript levels of its gene MYL9 were decreased. Myosin IIA and MLC phosphorylation are important in platelet responses to activation and regulate thrombopoiesis by a negative regulatory effect on premature proplatelet formation. We addressed the hypothesis that MYL9 is a transcriptional target of RUNX1. Chromatin immunoprecipitation (ChIP) using megakaryocytic cells revealed RUNX1 binding to MYL9 promoter region -729/-542 basepairs (bp), which contains 4 RUNX1 sites. Electrophoretic mobility shift assay showed RUNX1 binding to each site. In transient ChIP assay, mutation of these sites abolished binding of RUNX1 to MYL9 promoter construct. In reporter gene assays, deletion of each RUNX1 site reduced activity. MYL9 expression was inhibited by RUNX1 short interfering RNA (siRNA) and enhanced by RUNX1 overexpression. RUNX1 siRNA decreased cell spreading on collagen and fibrinogen. Our results constitute the first evidence that the MYL9 gene is a direct target of RUNX1 and provide a mechanism for decreased platelet MYL9 expression, MLC phosphorylation, thrombocytopenia, and platelet dysfunction associated with RUNX1 mutations.

Indexed as

Gene Expression RegulationBase SequenceBlood Platelet DisordersBlood PlateletsCells, CulturedCore Binding Factor Alpha 2 SubunitHumansMolecular Sequence DataMyosin Light ChainsPlatelet AggregationPromoter Regions, GeneticRNA, Small InterferingThrombocytopeniaCore Binding Factor Alpha 2 SubunitMyosin Light ChainsRNA, Small InterferingRUNX1 protein, human

Identifiers

PMID20876458
PMCPMC3031389
OpenAlexW2054749702

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.