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Supplementary Information

Identification of genes associated with chemotherapy cross-resistance and treatment response in childhood acute lymphoblastic leukemia.

Sanne Lugthart, Meyling H. Cheok, Monique L. den Boer, Wenjian Yang, Amy Holleman, Cheng Cheng, Ching-Hon Pui, Mary V. Relling, Gritta E. Janka-Schaub, Rob Pieters, William E. Evans


Supplementary Appendix 1

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

Table of Content

  • 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