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Blood, 15 March 2008, Vol. 111, No. 6, pp. 2984-2990. Prepublished online as a Blood First Edition Paper on January 8, 2008; DOI 10.1182/blood-2007-09-114082. This Article Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2007-09-114082v1 111/6/2984    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Davies, S. M Articles by Relling, M. V. Search for Related Content PubMed PubMed Citation Articles by Davies, S. M Articles by Relling, M. V. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 20, 2007 Accepted December 19, 2007 Pharmacogenetics of minimal residual disease response in children with Acute Lymphoblastic Leukemia (ALL): a report from the Children's Oncology Group Stella M Davies*, Michael J Borowitz, Gary L. Rosner, Kristin Ritz, Meenakshi Devidas, Naomi Winick, Paul L. Martin, Paul Bowman, James Elliott, Cheryl Willman, Soma Das, Edwin H. Cook, and Mary V. Relling Dept. of Pediatrics, Cincinnati Children's Hospital and Medical Center, Cincinnati, OH Dept of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD Dept of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX Statistics, Children's Oncology Group and University of Florida, Gainesville, FL Dept of Pediatrics,, UT Southwestern Medical Center, Dallas, TX Dept of Pediatrics, Duke University Medical Center, Durham, NC Dept of Pediatrics, Cook Children's Medical Center, Fort Worth, TX Dept of Pathology, New Mexico Cancer Center, Albuquerque, NM Dept. of Psychiatry, Human Genetics and Medicine, University of Illinois in Chicago, Chicago, IL Pharmaceutical Dept, St. Jude Children's Research Hospital, Memphis, TN * Corresponding author; email: stella.davies{at}cchmc.org. The presence of minimal residual disease (MRD) as a marker of antileukemic drug efficacy is being used to assess risk status and, in some cases, to adjust the intensity of therapy. Within known prognostic categories, the determinants of MRD are not yet known. We measured MRD by flow cytometry at day 8 (in blood) and at day 28 (in bone marrow) of remission induction therapy in over 1,000 children enrolled on Pediatric Oncology Group anti-metabolite based therapy protocols 9904, 9905, and 9906. We classified patients as "best risk" if they had cleared MRD by day 8 of therapy and as "worst risk" if they had MRD remaining in bone marrow at day 28, and tested whether MRD was related polymorphisms in 16 loci in genes hypothesized to influence response to therapy in ALL. After adjusting for known prognostic features such as the presence of the TEL-AML1 rearrangement, NCI risk status, ploidy and race, the G allele of a common polymorphism in chemokine receptor 5 (CCR5) was associated with a more favorable MRD status than the A allele (p = 0.009, logistic regression), when comparing "best" and "worst" risk groups. These data are consistent with the growing evidence that both acquired and host genetics influence response to cancer therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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