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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1042-1047. Prepublished online as a Blood First Edition Paper on May 16, 2008; DOI 10.1182/blood-2008-01-135970. This Article Full Text (PDF) Supplemental Methods and Figure All Versions of this Article: blood-2008-01-135970v1 112/4/1042    most recent Alert me when this article is cited Alert me if a correction is posted 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 Shinawi, M. Articles by Plon, S. E. Search for Related Content PubMed PubMed Citation Articles by Shinawi, M. Articles by Plon, S. E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 29, 2008 Accepted March 27, 2008 Syndromic thrombocytopenia and predisposition to acute myelogenous leukemia caused by constitutional microdeletions on chromosome 21q Marwan Shinawi, Ayelet Erez, Deborah L. Shardy, Brendan Lee, Rizwan Naeem, George Weissenberger, A. Craig Chinault, Sau Wai Cheung, and Sharon E. Plon* Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States Texas Children’s Cancer Center, Texas Children's Hospital, Houston, TX, United States Medical Genetics Laboratories, Baylor College of Medicine, Houston, TX, United States * Corresponding author; email: splon{at}bcm.edu. Several lines of evidence support the presence of dosage-sensitive genes on chromosome 21 that regulate leukemogenesis and hematopoiesis. We report a detailed clinical and molecular characterization of three patients with chronic thrombocytopenia caused by distinct constitutional microdeletions involving chromosomal region 21q22.12. The patients exhibited growth restriction, dysmorphic features, and developmental delays. One patient developed acute myelogenous leukemia (AML) at 6 years of age. All three deletions included the RUNX1, CLIC6, DSCR, and KCNE1 genes. Our data provide additional support for the role of RUNX1 haploinsufficiency in megakaryopoiesis and predisposition to AML. The leukemic clone had trisomy 21 resulting from duplication of chromosome 21 containing the RUNX1 deletion. This demonstrates that genes other than RUNX1 must also play a role in AML associated with trisomy 21. We recommend that children with syndromic thrombocytopenia have clinical array-comparative genomic hybridization analysis and appropriate cytogenetic studies to facilitate our ability to provide a definitive diagnosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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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