Different expression of glutathione S-transferase α, μ and π in childhood acute lymphoblastic and myeloid leukaemia

Expression of three major classes of glutathione S-transferases (GSTs), i.e. α, μ and π class, P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) were studied in childhood acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML) and normal peripheral blood lymphocytes by flow cytometry. In vitro cytotoxicity of 4-hydroxy-ifosfamide (IFOS), daunorubicin (DNR) and prednisolone (PRED) was assessed by the MTT assay. Expression of α, μ and π class GST did not significantly differ between leukaemic cells from 100 initial and 14 unrelated relapse ALL patients (GSTαP=0.26; GSTμP = 0.09; GSTπP = 0.13). The expression of GSTα (1.4-fold, P = 0.0004), GSTπ (1.3-fold, P = 0.001) and to a lesser extent also GSTμ (1.1-fold, P = 0.03) was higher in ALL compared with normal peripheral blood lymphocytes. Expression of GSTμ and GSTπ was significantly higher in 18 AML compared with 100 ALL patients at initial diagnosis (respectively 1.3-fold, P = 0.0005 and 2-fold, P < 0.0001). In contrast, GSTα was median 2-fold lower expressed in the AML samples (P < 0.0001). Expression levels of α, μ and π class GSTs were not related to the degree of resistance to IFOS, DNR and PRED nor to immunophenotype, white blood cell count or age at presentation of childhood ALL. One exception was a remarkably low expression of GSTα in IFOS-sensitive samples compared with a heterogenous expression in IFOS-resistant samples (P = 0.02). Expression of GSTπ, but not of GSTα or GSTμ, weakly correlated with the expression of MRP (Rs 0.36, P = 0.002, n = 74) but not with P-gp. However, a high expression of both GSTπ and MRP was not associated with in vitro resistance to IFOS, DNR or PRED. The present data suggest that expression of GSTs is not linked to the degree of resistance to IFOS, DNR and PRED or clinical risk factors in childhood ALL. Whether the high expression of GSTμ and GSTπ in AML cells contributes to the relative resistance to IFOS, DNR and PRED compared with ALL samples (P  0.0001) warrants further study.