Supplementary Information for: Identification of genes associated with chemotherapy cross-resistance and treatment response in childhood acute lymphoblastic leukemia. Sanne Lugthart 1,2,6,8 , Meyling H. Cheok 1,2,8 , Monique L. den Boer 6 , Wenjian Yang 1,2,5 , Amy Holleman 6 , Cheng Cheng 3 , Ching-Hon Pui 1,4,5 , Mary V. Relling 1,2,5 , Gritta E. Janka-Schaub 7 , Rob Pieters 6,9 , William E. Evans 1,2,5,9 1 Hematological Malignancy Program 2 Department of Pharmaceutical Sciences 3 Department of Biostatistics 4 Department of Hematology-Oncology ,St. Jude Children's Research Hospital , Memphis , USA 5 The Pharmacogenetics of Anticancer Agents Research Group in the Pharmacogenetics Research Network, Memphis , Tennessee , USA 6 Department of Pediatric Oncology/Hematology ,Erasmus University Medical Center/Sophia Children's Hospital, ,Rotterdam , The Netherlands 7 COALL study group ,Children's University Hospital , Hamburg , Germany 8 These first authors contributed equally to this work. 9 These last authors contributed equally to this work.

Supplemental Table 1: Characteristics of patients within each group classified as cross-resistant and VCR-ASP discordant resistant ALL.

The ALL subtypes of the 129 patients for whom gene expression was performed included 40 with the TEL-AML1 gene fusion t(12;21), 33 hyperdiploid (>50 chromosomes), six with the E2A-PBX1 gene fusion t(1;19), five with the BCR-ABL gene fusion t(9;22) and three with the MLL-AF4 gene fusion  t(4;11). The remaining 40 B-lineage ALLs were negative for all five of these genetic subtypes. White blood cell count at diagnosis (WBC), age at diagnosis and sex in patients defined as cross-resistant (n=29) or cross-sensitive (n=38) by the CR-score. Patients with VCR-sensitive plus ASP-resistant ALL (VCR-S+ASP-R, n=42) or VCR-resistant ALL plus ASP-sensitive (VCR-R+ASP-S, n=34), as defined by the VCR-ASP discordant resistance phenotype. TEL-AML1 translocation and hyperdiploidy showed a trend of higher prevalence in younger children, but was not statistically significant in our population (P=0.1074, ANOVA). Sixteen of 34 (47%) ALLs that were VCR-resistant plus ASP-sensitive compared to only three of 42 (7%) that were VCR-sensitive plus ASP-resistant, had the t(12;21) translocation yielding the TEL-AML1 gene fusion (P=0.0001, Fisher's exact test). Fifteen of 34 (44%) ALLs that were VCR-resistant plus ASP-sensitive, compared to only four of 42 (10%) that were VCR-sensitive plus ASP-resistant, were hyperdiploid (P=0.001, Fisher's exact test). All 19 TEL-AML1 positive and 19 hyperdiploid ALLs grouped together in one branch in the hierarchical clustering using the 200 probe sets discriminating VCR-ASP-discordant resistance (Supplemental Figure 6A).