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Blood, 1 December 2008, Vol. 112, No. 12, pp. 4639-4645. Prepublished online as a Blood First Edition Paper on August 21, 2008; DOI 10.1182/blood-2008-05-156745. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-05-156745v1 112/12/4639    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Owen, C. J. Articles by Fitzgibbon, J. Search for Related Content PubMed PubMed Citation Articles by Owen, C. J. Articles by Fitzgibbon, J. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Five new pedigrees with inherited RUNX1 mutations causing familial platelet disorder with propensity to myeloid malignancy Carolyn J. Owen1,2, Cynthia L. Toze2, Anna Koochin2, Donna L. Forrest2, Clayton A. Smith2, Jane M. Stevens1, Shannon C. Jackson3, Man-Chiu Poon3, Gary D. Sinclair4, Brian Leber5, Peter R. E. Johnson6, Anthony Macheta7, John A. L. Yin8, Michael J. Barnett2, T. Andrew Lister1, and Jude Fitzgibbon1 1 Centre for Medical Oncology, Barts and the London School of Medicine & Dentistry, London, United Kingdom; 2 Leukemia/BMT Program of British Columbia, British Columbia Cancer Agency and Vancouver General Hospital, and University of British Columbia, Vancouver, BC; 3 Division of Hematology and Hematologic Malignancies, Department of Medicine, University of Calgary, and Calgary Health Region, Calgary, AB; 4 Department of Biochemistry and Molecular Biology, University of Calgary, and Molecular Hematology, Calgary Laboratory Services, Calgary, AB; 5 Department of Biochemistry & Biomedical Sciences, McMaster University, Hamilton, ON; 6 Department of Haematology, Western General Hospital, Edinburgh, United Kingdom; 7 Furness General Hospital, University Hospitals of Morecambe Bay NHS Trust, Morecambe Bay, United Kingdom; and 8 University Department of Haematology, Manchester Royal Infirmary, Manchester, United Kingdom Familial platelet disorder with propensity to myeloid malignancy (FPD/AML) is an autosomal dominant syndrome characterized by platelet abnormalities and a predisposition to myelodysplasia (MDS) and/or acute myeloid leukemia (AML). The disorder, caused by inherited mutations in RUNX1, is uncommon with only 14 pedigrees reported. We screened 10 families with a history of more than one first degree relative with MDS/AML for inherited mutations in RUNX1. Germ- line RUNX1 mutations were identified in 5 pedigrees with a 3:2 predominance of N-terminal mutations. Several affected members had normal platelet counts or platelet function, features not previously reported in FPD/AML. The median incidence of MDS/AML among carriers of RUNX1 mutation was 35%. Individual treatments varied but included hematopoietic stem cell transplantation from siblings before recognition of the inherited leukemogenic mutation. Transplantation was associated with a high incidence of complications including early relapse, failure of engraftment, and posttransplantation lymphoproliferative disorder. Given the small size of modern families and the clinical heterogeneity of this syndrome, the diagnosis of FPD/AML could be easily overlooked and may be more prevalent than previously recognized. Therefore, it would appear prudent to screen young patients with MDS/AML for RUNX1 mutation, before consideration of sibling hematopoietic stem cell transplantation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Huang, M. Yu, T. E. Akie, T. B. Moran, A. J. Woo, N. Tu, Z. Waldon, Y. Y. Lin, H. Steen, and A. B. Cantor Differentiation-Dependent Interactions between RUNX-1 and FLI-1 during Megakaryocyte Development Mol. Cell. Biol., August 1, 2009; 29(15): 4103 - 4115. [Abstract] [Full Text] [PDF] C. Preudhomme, A. Renneville, V. Bourdon, N. Philippe, C. Roche-Lestienne, N. Boissel, N. Dhedin, J.-M. Andre, P. Cornillet-Lefebvre, A. Baruchel, et al. High frequency of RUNX1 biallelic alteration in acute myeloid leukemia secondary to familial platelet disorder Blood, May 28, 2009; 113(22): 5583 - 5587. [Abstract] [Full Text] [PDF]

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