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Supplementary Information

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

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

Mercaptopurine (MP) in vitro resistance, tested at St. Jude cells of additional patients enrolled on Total Therapy XV protocol (SJCRH) and MP in vitro resistance tested in a subset of patients of the COALL/DCOG patients, were significantly related to the new cross-resistance gene expression score (GE CR). Additionally, resistance to MP was not related to the VCR-ASP discordant resistance gene expression score (GE VA) and more importantly, no association was found for MP resistance with the combined single-drug resistance gene expression score (GE PDAV) (Holleman, NEJM, 2004). This indicates that cross-resistance indeed reflects a common resistance mechanism that relates to multiple antileukemic drugs, beyond the four drugs we studied, that is distinct from our prior combined single-drug resistance gene expression signature (sum of PDAV).

COALL/DCOG
MP n=29
SJCRH
MP n=51
P-value* rho* P-value* rho*
GE CR 0.0002 0.64 0.007 0.37
GE VA 0.54 0.12 0.13 0.22
GE PVAD 0.99 0.002 0.06 0.27

*Spearman rank correlation, P-value, coefficient (rho)

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