Author Contributions: Dr Relling had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: J. Yang, Cheng, Evans, Camitta, Willman, Carroll, Relling.
Acquisition of data: W. Yang, Pei, Neale, French, Campana, Downing, Evans, Pui, Devidas, Bowman, Willman, Borowitz, Hunger, Relling.
Analysis and interpretation of data: J. Yang, Cheng, Pei, Cao, Fan, Pounds, Treviño, Evans, Camitta, Willman, Davies, Carroll, Hunger, Relling.
Drafting of the manuscript: J. Yang, Evans, Camitta, Willman, Relling.
Critical revision of the manuscript for important intellectual content: J. Yang, Cheng, W. Yang, Pei, Cao, Fan, Pounds, Neale, Treviño, French, Campana, Downing, Evans, Pui, Devidas, Bowman, Camitta, Davies, Borowitz, Carroll, Hunger, Relling.
Statistical analysis: J. Yang, Cheng, W. Yang, Pei, Cao, Fan, Pounds, Devidas.
Obtained funding: Campana, Evans, Davies, Borowitz, Carroll, Relling.
Administrative, technical, or material support: Neale, Treviño, French, Campana, Downing, Evans, Pui, Carroll, Hunger, Relling.
Study supervision: Hunger, Relling.
Financial Disclosures: Dr Cheng serves on the Data Safety Monitoring Board for Enzon Pharmaceuticals, for which he is compensated. St Jude Children's Research Hospital allocates a portion of the income it receives from licensing inventions and tangible research materials to those researchers responsible for creating this intellectual property. Under this policy, Drs Evans and Relling report that they receive a portion of the income St Jude receives from licensing patent rights related to TPMT polymorphisms and GGH polymorphisms. Dr Pui has received honoraria for lectures and scientific consultation from Sanofi-Aventis. Dr Borowitz reports that he has been a consultant for and receives support in kind from BD Biosciences and research support from Genzyme. Dr Relling reports that she is on the Scientific Advisory Board for Genome Explorations (uncompensated) and that she will likely soon receive funding for investigator-initiated research on the pharmacology of asparaginase from Enzon Pharmaceuticals. No other financial disclosures were reported.
Funding/Support: This work was supported by grants CA 093552-02, CA 51001, CA 78224, CA 21765, CA R3736401, CA 60419, CA 086011, CA 98543, CA 29139, and National Institutes of Health (NIH)/National Institute of General Medical Sciences (NIGMS) Pharmacogenetics Research Network and Database grants U01 GM61393 and U01 GM61374 (http://www.pharmgkb.org) from the National Cancer Institute and NIGMS; by the American Lebanese Syrian Associated Charities; and by CureSearch.
Role of the Sponsor: The NIH, CureSearch, and American Lebanese Syrian Associated Charities provided financial support for the clinical St Jude Total Therapy protocols XIIIB and XV and the COG P9906 trial, as well as for the genetic studies. These sponsors were not directly involved in design, conduct of study, or genomic data collection/management/analysis or review/approval of the manuscript.
Additional Contributions: We are indebted to all patients and their parents who participated St Jude Total Therapy protocols XIIIB and XV and the COG P9906 study, the clinicians and research staff at the St Jude and COG institutions, Jeannette Pullen, MD (University of Mississippi Medical Center, Children's Hospital, Jackson), and Andrew Carroll, PhD (Department of Genetics, University of Alabama at Birmingham), for assistance in classification of patients with ALL (both of whom were partially compensated by NIH grants supporting this work), and Tianhe Zhang (St Jude Children's Research Hospital) for his help in data analysis (who was compensated by St Jude for his work).