St. Jude Children's Research: ALL5

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.

Supplementary Appendix 1

This appendix has been provided by the authors to give readers additional information about their work

Table of Contents

pdf
(1.2mb)

doc
(3.23mb)

data files
(zipped cel files)

group 1 (62mb - 20 files)
group 2 (60mb - 20 files)
group 3 (61mb - 20 files)
group 4 (62mb - 20 files)
group 5 (62mb - 20 files)
group 6 (90mb - 29 files)

metric data files
(txt files)

analysis info

call.txt (5.8mb)

data.txt (18mb)

p value (24.8mb)

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

Supplemental Table 2: False discovery rate.

Supplemental Table 3: Cross-validation using gene expression scores for cross-resistance and VCR-ASP discordant resistance.

Supplemental Table 4: Transcription factor motifs over-represented in the set of genes over-expressed in cross-resistant versus cross-sensitive ALL.

Supplemental Table 5: Genes discriminating VCR-ASP discordant resistance in pediatric B-lineage ALL.

Supplemental Table 6: Transcription factor binding sites over-represented in the sub-cluster of genes over-expressed in VCR-ASP discordant resistant ALL.

Supplemental Table 7: Overlap of genes discriminating multiple-drug resistance and genes discriminating ALL subtypes

Supplemental Table 8: Overlap in genes discriminating multiple-drug cross-resistance and genes discriminating PRD-, VCR-, ASP- and DNR single-drug resistance.

Supplemental Table 9: Overlap in genes discriminating VCR-ASP discordant resistance and genes discriminating VCR- and ASP single-drug resistance.

Supplemental Table 10: Proportional-hazards regression analysis.

Supplemental Table 11: The multiple-drug cross-resistance gene expression score is significantly predictive of resistance of other antileukemic agents.

Supplemental Figure 1: Correlation of in vitro sensitivity of primary ALL cells.

Supplemental Figure 2: Distribution of cross-resistance (CR-scores) and VCR-ASP discordant resistance scores (VCR-ASP-score) in B-lineage ALL patients.

Supplemental Figure 3: Distribution of LC 50 values for each drug tested in the CR-group and VCR-ASP group analyzed for gene expression.

Supplemental Figure 4: Principal component analysis plot of genes discriminating cross-resistance and VCR-ASP discordant resistance.

Supplemental Figure 5: Gene Ontology (GO) of genes discriminating cross-resistance and genes discriminating VCR-ASP discordant resistance.

Supplemental Figure 6: Hierarchical clustering of ALL patients using genes discriminating cross-resistance and VCR-ASP discordant resistance.

Supplemental Figure 7: Hierarchical clustering using ALL subtype adjusted genes that discriminate VCR-ASP discordant resistance.

Supplemental Figure 8: Treatment outcome among VCR-ASP discordant resistant B-lineage ALL patients using the adjusted gene expression score.

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