Evidence map›Paper›PMID 17392504›Full record

ArticleBlood2007

The May-Hegglin anomaly gene MYH9 is a negative regulator of platelet biogenesis modulated by the Rho-ROCK pathway.

Zhao Chen, Olaia Naveiras, Alessandra Balduini, Akiko Mammoto, Mary Anne Conti, Robert S Adelstein, Donald Ingber, George Q Daley, Ramesh A Shivdasani

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
6.8field-weighted citation impact, top 3% 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

66 citing papers in PubMed, 163 citations in OpenAlex.

  1. Trial
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  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Non-Muscle Myosin II A: Friend or Foe in Cancer?International journal of molecular sciences · 2024
    Review
  10. Article
  11. Inside-to-outside and back to the future of megakaryopoiesis.Research and practice in thrombosis and haemostasis · 2023
    Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Myosin Heavy Chain 9: Oncogene or Tumor Suppressor Gene?Medical science monitor : international medical journal of experimental and clinical research · 2019
    Review
  20. Article

6 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

9 authors at 5 institutions in 2 countries.

Zhao ChenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Olaia Naveiras
Alessandra Balduini
Akiko Mammoto
Mary Anne Conti
Robert S Adelstein
Donald Ingber
George Q Daley
Ramesh A Shivdasani
Boston Children's Hospital · USDana-Farber Cancer Institute · USHarvard University · USNational Heart Lung and Blood Institute · USUniversity of Pavia · IT

Funding

NFE2 AND BETA 1 TUBULIN IN PLATELET DIFFERENTIATIONR01HL063143 · NHLBI · DANA-FARBER CANCER INSTITUTE · PI SHIVDASANI, RAMESH A · 1999 to 2012
$4.5M
In Vivo Function of Nonmuscle Myosin II-AZ01HL004218 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI ADELSTEIN, ROBERT · 1991 to 2008
$826k
Cellular and Molecular Regulation of ThrombopoiesisR56HL063143 · NHLBI · DANA-FARBER CANCER INST · PI SHIVDASANI, RAMESH A · 2008 to 2008
$428k
NCI NIH HHS CA55883NHLBI NIH HHS HL63143NHLBI NIH HHS R01 HL063143NHLBI NIH HHS R56 HL063143Telethon GGP06177
6 · The paper itself

Abstract

The gene implicated in the May-Hegglin anomaly and related macrothrombocytopenias, MYH9, encodes myosin-IIA, a protein that enables morphogenesis in diverse cell types. Defective myosin-IIA complexes are presumed to perturb megakaryocyte (MK) differentiation or generation of proplatelets. We observed that Myh9(-/-) mouse embryonic stem (ES) cells differentiate into MKs that are fully capable of proplatelet formation (PPF). In contrast, elevation of myosin-IIA activity, by exogenous expression or by mimicking constitutive phosphorylation of its regulatory myosin light chain (MLC), significantly attenuates PPF. This effect occurs only in the presence of myosin-IIA and implies that myosin-IIA influences thrombopoiesis negatively. MLC phosphorylation in MKs is regulated by Rho-associated kinase (ROCK), and consistent with our model, ROCK inhibition enhances PPF. Conversely, expression of AV14, a constitutive form of the ROCK activator Rho, blocks PPF, and this effect is rescued by simultaneous expression of a dominant inhibitory MLC form. Hematopoietic transplantation studies in mice confirm that interference with the putative Rho-ROCK-myosin-IIA pathway selectively decreases the number of circulating platelets. Our studies unveil a key regulatory pathway for platelet biogenesis and hint at Sdf-1/CXCL12 as one possible extracellular mediator. The unexpected mechanism for Myh9-associated thrombocytopenia may lead to new molecular approaches to manipulate thrombopoiesis.

Indexed as

ThrombopoiesisAnimalsBlood PlateletsEmbryonic Stem CellsHumansIntracellular Signaling Peptides and ProteinsMegakaryocytesMiceMyosin Light ChainsNonmuscle Myosin Type IIAPhosphorylationProtein Serine-Threonine Kinasesrho-Associated KinasesIntracellular Signaling Peptides and ProteinsMyosin Light ChainsNonmuscle Myosin Type IIAProtein Serine-Threonine Kinasesrho-Associated Kinases

Identifiers

PMID17392504
PMCPMC1896110
OpenAlexW1969318465

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.