Supplementary Information

Gene-expression patterns in drug resistant acute lymphoblastic leukemia cells and response to treatment.

Amy Holleman, Meyling H. Cheok, Monique L. den Boer, Wenjian Yang, Anjo J.P. Veerman, Karin M. Kazemier, Deqing Pei, Cheng Cheng, Ching-Hon Pui, Mary V. Relling, Gritta E. Janka-Schaub, Rob Pieters, and William E. Evans

N Engl J Med. 2004 Aug 5;351(6):533-42.

Table of Content

• Supplemental Figure 1:
  Unsupervised hierarchical clustering discriminating drug resistant and drug sensitive ALL patients.

• Supplemental Figure 2:
  Data analysis flowchart.

• Supplemental Figure 3:
  Supervised hierarchical clustering discriminating drug resistant and drug sensitive ALL patients (B- and T-lineage ALL).

• Supplemental Figure 4:
  Principal component analysis of drug resistant and sensitive ALL samples for the four antileukemic agents (B- and T-lineage ALL).

• Supplemental Figure 5:
  Supervised hierarchical clustering discriminating prednisolone resistant and sensitive B-lineage ALL.

• Supplemental Figure 6:
  Supervised hierarchical clustering discriminating vincristine resistant and sensitive B-lineage ALL.

• Supplemental Figure 7:
  Supervised hierarchical clustering discriminating L-asparaginase resistant and sensitive B-lineage ALL.

• Supplemental Figure 8:
  Supervised hierarchical clustering discriminating daunorubicin resistant and sensitive B-lineage ALL.

• Supplemental Figure 9:
  Supervised hierarchical clustering discriminating prednisolone resistant and sensitive ALL (B- and T-lineage ALL).

• Supplemental Figure 10:
  Supervised hierarchical clustering discriminating vincristine resistant and sensitive ALL (B- and T-lineage ALL).

• Supplemental Figure 11:
  Supervised hierarchical clustering discriminating L-asparaginase resistant and sensitive ALL (B- and T-lineage ALL).

• Supplemental Figure 12:
  Supervised hierarchical clustering discriminating daunorubicin resistant and sensitive ALL (B- and T-lineage ALL).

• Supplemental Figure 13:
  Gene Ontology classification of genes discriminating drug resistance in patients with acute lymphoblastic leukemia (B- and T-lineage ALL).

• Supplemental Figure 14:
  Pathway analysis of genes associated with L-asparaginase resistance in B-lineage ALL.

• Supplemental Table 1:
  LC₅₀ values for classification of resistant and sensitive ALL for each chemotherapeutic agent.

• Supplemental Table 2:
  Patient characteristics.

• Supplemental Table 3:
  Permutation analysis and false discovery rate of probe sets selected by Wilcoxon rank sum test and t-test.

• Supplemental Table 4:
  Number of significant probe sets discriminating drug resistance for each individual antileukemic agent.

• Supplemental Table 5:
  Prediction accuracy using gene expression profiles for classification of drug resistant and sensitive acute lymphoblastic leukemia. 9

• Supplemental Table 6:
  Gene expression scores for the intermediate sensitivity group, using genes selected to discriminate resistant and sensitive B-lineage ALL.

• Supplemental Table 7:
  Genes previously linked to drug resistance or prognosis in ALL.

• Supplemental Table 8:
  Multivariate analysis of gene expression and known prognostic factors (age, WBC count) to discriminate in vitro drug resistance.

• Supplemental Table 9:
  Association of the LC50 scores with gene expression scores and other known prognostic variables.

• Supplemental Table 10:
  Association of the drug resistance gene expression scores and minimal residual disease (MRD).

• References