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Blood, 1 May 2008, Vol. 111, No. 9, pp. 4496-4499. Prepublished online as a Blood First Edition Paper on February 19, 2008; DOI 10.1182/blood-2007-11-123885. This Article Full Text (PDF) All Versions of this Article: blood-2007-11-123885v1 111/9/4496    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 French, D. Articles by Relling, M. V Search for Related Content PubMed PubMed Citation Articles by French, D. Articles by Relling, M. V Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 14, 2007 Accepted February 14, 2008 A PAI-1 (SERPINE1) polymorphism predicts osteonecrosis in children with acute lymphoblastic leukemia: a report from the Children's Oncology Group Deborah French, Leo H Hamilton, Leonard A Mattano Jr, Harland N Sather, Meenakshi Devidas, James B Nachman, and Mary V Relling* Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN, United States Pediatric Hematology/Oncology, Michigan State University/Kalamazoo Center for Medical Studies, Kalamazoo, MI, United States Children's Oncology Group (COG), Arcadia, CA, United States Department of Pediatric Hematology-Oncology, University of Chicago, Chicago, IL, United States University of Tennessee, Memphis, TN, United States * Corresponding author; email: mary.relling{at}stjude.org. As glucocorticoid use increased in acute lymphoblastic leukemia, osteonecrosis became an increasingly frequent complication. Besides increased age, host risk factors are poorly defined. We tested whether 12 polymorphisms were associated with osteonecrosis among patients 10 years treated on the CCG1882 protocol. Candidate genes (TYMS, MTHFR, ABCB1, BGLAP, ACP5, LRP5, ESR1, PAI-1, VDR, PTH, and PTHR) were chosen based on putative mechanisms underlying osteonecrosis risk. All children received dexamethasone, with doses varying by treatment arm. A PAI-1 polymorphism (rs6092) was associated with risk of osteonecrosis in univariate (p=0.00205; odds ratio=2.79) and multivariate (p=0.001799; odds ratio=2.89) analyses (adjusting for gender, age, and treatment arm). Overall, 21 of 78 (26.9%) children with PAI-1 GA/AA genotypes, versus 25 of 214 (11.7%) children with GG genotype, developed osteonecrosis. PAI-1 polymorphisms and PAI-1 serum levels have previously been associated with thrombosis. We conclude PAI-1 genetic variation may contribute to risk of osteonecrosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. L. te Winkel, I. M. Appel, R. Pieters, and M. M. van den Heuvel-Eibrink Impaired dexamethasone-related increase of anticoagulants is associated with the development of osteonecrosis in childhood acute lymphoblastic leukemia Haematologica, October 1, 2008; 93(10): 1570 - 1574. [Abstract] [Full Text] [PDF]

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