Gene expression profile unravels significant differences between childhood and adult Ph+ acute lymphoblastic leukemia

The glutathione S-transferase (GSTs) superfamily of enzymes catalyzes the conjugation of xenobiotics and potentially damaging oxidative metabolites with glutathione. Four major subfamilies of GSTs (, , , ) can be distinguished in humans. Several studies implicate GST polymorphisms in de novo cancer as well as cancers that are secondary to chemotherapy. In all cases, GST deficiency, rather than high GST activity, has been associated with an increased risk of cancer. However, because of its activity, GST has been associated with cancer-drug resistance, while GST deficiency of GSTT1 and GSTM1 could positively influence chemotherapeutic efficacy in some patients.1 In the case of childhood acute lymphoblastic leukemia (ALL), conflicting results have been reported on the associations between GSTM1 and GSTT1 genotypes and outcome.2,3 Stanulla et al.4 recently showed a two-fold and 2.8-fold reduction in risk of relapse, respectively, relative to the presence of the GSTM1 or GSTT1. These findings encouraged the evaluation of the GST genotypes contribution to therapeutic outcome in larger, well-characterized ALL patient populations prospectively enrolled in the same protocol treatment.