Different expression of glutathione S-transferase alpha, mu and pi in childhood acute lymphoblastic and myeloid leukaemia

Expression of three major classes of glutathione S-transferases (GSTs), i.e . alpha, mu and pi class, P-glycoprotein (P-gp) and multidrug resistance-as sociated protein (MRP) were studied in childhood acute lymphoblastic leukae mia (ALL), acute myeloid leukaemia (AML) and normal peripheral blood lympho cytes by flow cytometry. In vitro cytotoxicity of 4-hydroxy-ifosfamide (IFO S), daunorubicin (DNR) and prednisolone (PRED) was assessed by the MTT assa y. Expression of alpha, mu and pi class GST did not significantly differ be tween leukaemic cells from 100 initial and 14 unrelated relapse ALL patient s (GST alpha P = 0.26; GST mu P = 0.09; GST pi P = 0.13). The expression of GST alpha (1.4-fold, P = 0.0004), GST pi (1.3-fold, P = 0.001) and to a le sser extent also GST mu (1.1-fold, P = 0.03) was higher in ALL compared wit h normal peripheral blood lymphocytes. Expression of GST mu and GST pi was significantly higher in 18 AML compared with 100 ALL patients at initial di agnosis (respectively 1.3-fold, P = 0.0005 and 2-fold, P < 0.0001). In cont rast, GST alpha was median 2-fold lower expressed in the AML samples (P < 0 .0001). Expression levels of alpha, mu and pi class GSTs were not related t o the degree of resistance to IFOS, DNR and PRED nor to immunophenotype, wh ite blood cell count or age at presentation of childhood ALL. One exception was a remarkably low expression of GST alpha in IFOS-sensitive samples com pared with a heterogenous expression in IFOS-resistant samples (P = 0.02). Expression of GST pi, but not of GST alpha or GST mu, weakly correlated wit h the expression of MRP (Rs 0.36, P = 0.002, n = 74) but not with P-gp. How ever, a high expression of both GST pi and MRP was not associated with in v itro resistance to IFOS, DNR or PRED. The present data suggest that express ion of GST pi is not linked to the degree of resistance to IFOS, DNR and PR ED or clinical risk factors in childhood ALL. Whether the high expression o f GST mu and GST pi in AML cells contributes to the relative resistance to IFOS, DNR and PRED compared with ALL samples (P less than or equal to 0.000 1) warrants further study.