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Supplementary Information

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

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

The relation of the combined LC50 score (by MTT assay) to disease-free survival was assessed in a univariate analysis. This revealed that in this cohort of patients (COALL/DCOG), PVAD LC50 score was not statistically significant at the P<0.05 level (intermediate LC50 score: hazard ratio =1.7, P=0.27; high LC50 score: hazard ratio =2.12, P=0.14), whereas the combined gene expression (GE) score was significantly associated with disease-free survival (intermediate GE score hazard ratio =2.34, P=0.07; high GE score hazard ratio =3.8, P=0.0023). The combined LC50 score and the combined gene expression score are significantly correlated with each other (R=0.69, P-value<0.0001, Pearson correlation), and thus can confound each other in a multivariate analysis.

The table below summarizes results of a multivariate analysis in which LC50 values, gene expression scores, and other known prognostic variables (patient age, WBC at diagnosis) were all included in the model to assess their relation to treatment outcome (disease free survival). As shown, WBC (>100x109/L) and gene expression score were statistically related to treatment outcome, whereas patient age is marginally significant, and LC50 scores are not.

Variable Hazard Ratio(95% C.I.) P-value
Age (years) 1.08 (1.0, 1.17) 0.054
WBC (109/L) 1.48 (1.15, 1.91) 0.0024
Combined drug resistance LC50 score 0.91 (0.75, 1.10) 0.310
Combined drug resistance gene expression score 1.78 (1.10, 2.80) 0.016

for prednisolone, vincristine, asparaginase, daunorubicin

In a multivariate analysis in which the four LC50 scores for each patient were included in the analysis along with drug resistance GE score, the GE score was marginally significant (intermediate GE score hazard ratio =2.37, P=0.098; high GE score hazard ratio =2.85, P=0.072).

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