1. Genome-wide association study identifies germline polymorphisms associated with relapse of childhood acute lymphoblastic leukemia
by Jun J. Yang, Cheng Cheng, Meenakshi Devidas, Xueyuan Cao, Dario Campana, Wenjian Yang, Yiping Fan, Geoff Neale, Nancy Cox, Paul Scheet, Michael J. Borowitz, Naomi J. Winick, Paul L. Martin, W. Paul Bowman, Bruce Camitta, Gregory H. Reaman, William L. Carroll, Cheryl L. Willman, Stephen P. Hunger, William E. Evans, Ching-Hon Pui, Mignon Loh, and Mary V. Relling
Blood
Volume 120(20):
November 15, 2012
©2012 by American Society of Hematology

2. Iterative resampling approach to identify 134 SNPs reproducibly associated with ALL relapse.
Iterative resampling approach to identify 134 SNPs reproducibly associated with ALL relapse. A total of 2535 children with newly diagnosed ALL were split into a discovery and a validation cohort at a 1:1 ratio with balanced representation of treatment and clinical features. GWAS was performed on the discovery cohort and then on filtered SNPs based on replication in the remaining patients (replication cohort). Resampling was performed for 100 iterations and 134 SNPs were selected as “relapse SNPs” because they were successfully replicated in multiple rounds of resampling. Ip indicates information profiling (see “GWAS for germline SNP genotypes related to risk of relapse”).
Jun J. Yang et al. Blood 2012;120:
©2012 by American Society of Hematology

3. Association of genotypes at the PYGL SNP (rs7142143) with the risk of ALL relapse.
Association of genotypes at the PYGL SNP (rs ) with the risk of ALL relapse. The cumulative incidence of any relapse was compared for each genotype group at rs (CC/CT or TT) in all patients (A) and in those patients negative for MRD at the end of remission induction (B). The P value was estimated using the Fine and Gray hazard regression model.
Jun J. Yang et al. Blood 2012;120:
©2012 by American Society of Hematology

4. An example of relapse-associated SNPs affecting pharmacokinetics and pharmacodynamics of antileukemic agents.
An example of relapse-associated SNPs affecting pharmacokinetics and pharmacodynamics of antileukemic agents. Genotype at ABCB1 SNP rs is associated with both ALL relapse (A) and dexamethasone apparent oral plasma clearance (B). Note that the C allele is linked to lower dexamethasone clearance and also lower cumulative incidence of relapse. The association of SNP genotype with clearance and with relapse was estimated by linear regression and the Fine and Gray hazard regression model, respectively. Dexamethasone clearance was determined in St Jude Total XV protocol at week 7 of continuation therapy, which is shown for those in the standard-/high-risk arm.
Jun J. Yang et al. Blood 2012;120:
©2012 by American Society of Hematology