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Supplementary Information

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

References

To test the relation between the combined drug resistance gene expression score (GE score) and the presence (=0.01 percent) or absence (=0.01 percent) of minimal residual disease (MRD) on day 19 of treatment and on day 43 (end of induction), we used MRD data that were available for a subset of the SJCRH cohort (independent test set). MRD results were available on 33 patients on day 19 and 44 patients on day 43. Despite the small number of patients for whom both MRD and gene expression were available in our cohort, there was an association between the GE score and MRD on day 19 (a), with a resistant (high) GE score associated with presence of MRD  (P=0.10, Wicoxon rank sum test). In contrast, there was no evidence of an association between the GE score and MRD on day 43 (b) (P=0.52, Wicoxon rank sum test). The predominant components of treatment were prednisolone, vincristine, asparaginase and daunorubicin (PVAD) during the first 19 days, whereas etoposide and cytarabine were also given between days 19 and 43, consistent with the GE score being an important predictor of disease response to these four agents (i.e., day 19 MRD). Over the entire course of treatment (2.5 to 3 years) PVAD constituted a substantially greater proportion of treatment than other agents such as etoposide and cytarabine, consistent with GE score being significantly related to long term outcome, as observed in the training set and the independent test set.

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