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MYH10 protein expression in platelets as a biomarker of RUNX1 and FLI1 alterations.

Abstract
RUNX1 gene alterations are associated with acquired and inherited hematologic malignancies that include familial platelet disorder/acute myeloid leukemia, primary or secondary acute myeloid leukemia, and chronic myelomonocytic leukemia. Recently, we reported that RUNX1-mediated silencing of nonmuscle myosin heavy chain IIB (MYH10) was required for megakaryocyte ploidization and maturation. Here we demonstrate that runx1 deletion in mice induces the persistence of MYH10 in platelets, and a similar persistence was observed in platelets of patients with constitutional (familial platelet disorder/acute myeloid leukemia) or acquired (chronic myelomonocytic leukemia) RUNX1 mutations. MYH10 was also detected in platelets of patients with the Paris-Trousseau syndrome, a thrombocytopenia related to the deletion of the transcription factor FLI1 that forms a complex with RUNX1 to regulate megakaryopoiesis, whereas MYH10 persistence was not observed in other inherited forms of thrombocytopenia. We propose MYH10 detection as a new and simple tool to identify inherited platelet disorders and myeloid neoplasms with abnormalities in RUNX1 and its associated proteins.
AuthorsIléana Antony-Debré, Dominique Bluteau, Raphael Itzykson, Véronique Baccini, Aline Renneville, Françoise Boehlen, Margot Morabito, Nathalie Droin, Caroline Deswarte, Yunhua Chang, Guy Leverger, Eric Solary, William Vainchenker, Rémi Favier, Hana Raslova
JournalBlood (Blood) Vol. 120 Issue 13 Pg. 2719-22 (Sep 27 2012) ISSN: 1528-0020 [Electronic] United States
PMID22677128 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers
  • Core Binding Factor Alpha 2 Subunit
  • Proto-Oncogene Protein c-fli-1
  • Nonmuscle Myosin Type IIB
  • nonmuscle myosin type IIB heavy chain
  • Myosin Heavy Chains
Topics
  • Animals
  • Biomarkers (metabolism)
  • Blood Platelet Disorders (diagnosis, genetics, metabolism)
  • Blood Platelets (metabolism, pathology)
  • Case-Control Studies
  • Comparative Genomic Hybridization
  • Core Binding Factor Alpha 2 Subunit (physiology)
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Immunoblotting
  • Jacobsen Distal 11q Deletion Syndrome (diagnosis, genetics, metabolism)
  • Leukemia, Myeloid, Acute (diagnosis, genetics, metabolism)
  • Leukemia, Myelomonocytic, Chronic (diagnosis, genetics, metabolism)
  • Male
  • Megakaryocytes (pathology)
  • Mice
  • Myosin Heavy Chains (genetics, metabolism)
  • Nonmuscle Myosin Type IIB (genetics, metabolism)
  • Pedigree
  • Ploidies
  • Prognosis
  • Proto-Oncogene Protein c-fli-1 (genetics, metabolism)
  • Thrombocytopenia (diagnosis, genetics, metabolism)

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