Impact of glutathione S-transferase gene deletion on early relapse in childhood B-precursor acute lymphoblastic leukemia

Abstract

BACKGROUND AND OBJECTIVES: The glutathione-S-transferase (GST) polymorphism may affect the outcome of treatment of leukemia because GSTs play an important role in detoxifying the chemotherapeutic agents used to kill leukemia cells. However, results of previous reports have been controversial. This study was undertaken to clarify the influence of GST polymorphism on the outcome of childhood B-precursor acute lymphoblastic leukemia (ALL). DESIGN AND METHODS: Eighty-two patients with childhood B-precursor ALL treated during 1988-1999 with our ALL protocol (median follow-up time 89.5 months, range 31 -169 months) were examined for GST gene patterns. The effect of GSTM1 and GSTT1 deletion genotypes on the clinical features and therapeutic results was analyzed. RESULTS: All patients attained complete remission but 12 had an early relapse (within 30 months of the initiation of treatment). In univariate analysis, early relapse of ALL was correlated significantly with the presence of the t(9;22)(q34;q11) cytogenetic abnormality (p=0.0003), high white blood cell counts (p=0.015) and double null genotype (p=0.027). Multivariate analysis revealed that the GST double null genotype was the only significant independent predictor of early relapse (p=0.018). INTERPRETATION AND CONCLUSIONS: The simultaneous deletion of both the GSTM1 and GSTT1 genes is more predictive than any other parameter of early relapse of childhood B-precursor ALL.