[Anthracycline resistance: cytofluorometric study on infantile lymphoblastic leukemia]

Reduced intracellular drug retention has been recognized as a major characteristic of multidrug resistance (MDR) phenotype in a number of cell line models and has been associated to overexpression of a P-170 membrane glycoprotein. Although many studies have been performed on MDR cell lines, so far only few data have been presented utilizing fresh human tumor cells, leaving open the question of the relevance of reduction of intracellular drug exposure to clinical drug resistance. We chose to utilize blast cell samples obtained from patients with childhood acute lymphoblastic leukemia (ALL) to study their interaction with Doxorubicin (DX) and Daunorubicin (DN) as representative drugs, evaluating cellular drug uptake by flow cytometry. Aim of the work was to check possible difference of anthracycline fluorescence levels in clinically "potentially sensitive" (15 cases) and "potentially resistant" (11 cases) human leukemic blast cells. For this purpose, leukemic cells derived from peripheral blood of patients were exposed in vitro to DX and DN according to different schedules and analyses by flow cytometry. The calculated fluorescence levels associated with the different anthracycline treatment shows a wide interpatient spreading of values. The mean values in the potentially resistant group did not differ significantly from the mean values of the potentially sensitive group at any considered concentration, suggesting that biochemical mechanisms different from that involved in drug transport are responsible for the outcome of clinical drug resistance in childhood ALL.