chemotherapy cross-resistance and treatment response in childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) can be cured with combination chemotherapy in over 75% of children, but the cause of treatment failure in the remaining patients is unknown. We determined the sensitivity of ALL cells to individual antileukemic agents in 441 patients, and used a genome-wide approach to identify 45 genes differentially expressed in ALL exhibiting cross-resistance to prednisolone, vincristine, asparaginase and daunorubicin. We also identified a distinct phenotype of discordant resistance to asparaginase and vincristine and 139 genes whose expression was associated with this novel phenotype. The expression of these genes discriminated treatment outcome in two independent patient populations, identifying a subset of patients with a markedly inferior outcome (37%13% 5-year DFS).

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Lugthart S, Cheok MH, den Boer ML, Yang W, Holleman A, Cheng C, Pui CH, Relling MV, Janka-Schaub GE, Pieters R, Evans WE