Myeloid antigen co-expression in childhood acute lymphoblastic leukaemia: relationship with in vitro drug resistance

Contradictory data have been reported about the prognostic value of myeloid antigen co-expression (My(+)) in childhood acute lymphoblast ic leukaemia (ALL). In the present study the methyl thiazol tetrazoliumbromide (MTT) ass ay was used to compare the in vitro cytotoxicity of 14 drugs between 60 My( +) (CD13(+) and/or CD33(+)) and 107 My(-) ALL children at initial diagnosis . P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), maj or vault protein/lung resistance protein (LRP) and the intracellular daunor ubicin concentration were studied by flow cytometry. My(+) ALL samples were significantly more resistant, i.e. between 1.1- and 2.9-fold, to daunorubi cin, doxorubicin, idarubicin, mitoxantrone, vincristine, 6-thioguanine, 6-m ercaptopurine, teniposide, etoposide and ifosfamide compared with My(-) ALL samples. My(-) and My(+) ALL did not significantly differ in sensitivity t o prednisolone, dexamethasone, L-asparaginase and cytarabine. Comparable re sults were found when only common and preB ALL cases were analysed. Drug re sistance in My(+) ALL was not related to increased expression of P-gp, MRP or LRP compared with My(-) ALL (ratio My(+)/My(-):P-gp 0.8, MRP 1.0, LRP 1. 1). Accumulation and retention of daunorubicin did not significantly differ between My(-) and My(+) ALL cells (ratio My(+)/My(-): accumulation 1.2, re tention 1.3). Therefore the nature of drug resistance in My(+) ALL remains unknown, The lack of prognostic value for My(+) in childhood ALL map be exp lained by the responsiveness of My(+) ALL to glucocorticoids, L-asparaginas e and cytarabine. In addition, the currently intensive treatment regimens m ay apply drug doses which are simply high enough to overcome the mild resis tance to anthracyclines, mitoxantrone, vincristine, thiopurines, epipodophy llotoxins and ifosfamide in childhood My(+) ALL.