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 Figure 9: VCR-ASP discordant resistance adds predictive value related to relapse-free survival to single-drug resistance of PRD-VCR-ASP-DNR in patients with ALL.

Disease-free survival using the COALL/DCOG cohort (n=127) subdivided into equal groups (1/3) using the single PVAD resistance score (panel A). After stratification by PVAD, the worst group (n=41) was further divided into equal groups (1/2) by the VCR-ASP discordant resistance gene expression (VCR-ASP) score (panel B), revealing significant further discrimination by the VCR-ASP discordant resistance gene expression pattern. Shown is the disease-free survival in St. Jude patients (n=92), divided by the single PVAD resistance score defined by the COALL/DCOG cohort (panel C). After stratification by PDAV gene expression score, the worst group (n=19) was further divided into equal groups (1/2) by the multiple drug resistance (CR) gene expression score (panel D). After stratification by PVAD gene expression score, the worst group (n=19) was further sub-grouped (1/2) by the VCR-ASP discordant resistance gene expression score (panel D). Patients whose ALL cells exhibit a gene expression pattern indicative of both worst cross-resistance and worst VCR-ASP discordant resistance scores (i.e., the worst 25% of both CR- and VCR-ASP-scores are depicted in panel E. The 5-year treatment outcome of patients with both types of multiple-drug resistance (most unfavorable quartile for both CR and VCR-ASP) was 37%±13%, compared to 91%±9% in patients in the best quartile for both scores.

E