Expression of multidrug resistance (MDR) proteins and in vitro drug resistance in acute leukemias

Abstract

The expression of the multi drug resistance (MDR) proteins may influence the outcome of treatment in patients with acute leukemia. The aim of this study was to determine the IC₅₀ of cytotoxic drugs (cytosine arabinoside, ara-C and daunorubicin, dnr) using the in vitro 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-suljophenyl)2H-tetrazolium, inner salt (MTS) assay method. A total of 82 newly diagnosed acute leukemia cases (43 adult myeloid leukaemia, AML cases and 39 acute lymphoblastic leukaemia, ALL cases) and 16 relapsed cases (8 AML cases and 8 ALL cases) were studied. The MTS assay was performed using two cytotoxic drugs, dnr and ara-C. Cells were incubated with different concentrations of drugs for 4 days and the IC₅₀ was extrapolated from the viability curve. In newly diagnosed cases, we found that childhood ALL samples showed higher IC₅₀ values of dnr (0.040 ± 2.320) compared to adult AML samples (0.021 ± 0.158). In contrast, newly diagnosed adult AML samples showed higher IC₅₀ values of ara-C (0.157 ± 0.529) compared to childhood ALL samples (0.100 ± 2.350). In relapsed cases, two samples of childhood ALL showed IC₅₀ values of dnr (0.910 ± 1.760) and ara-C (1.310 ± 2.390), which was higher compared to childhood AML samples (0.129 ± 0.214 and 0.210 ± 0.003, respectively). However, there was no correlation between IC₅₀ values of these drugs tested with clinical outcome. In conclusion, we found that MTS assay is an easy, rapid and non laborious method to study in vitro drug resistance in acute leukaemia cases.

Keywords:

• MDR PROTEINS
• ABC SUPERFAMILY
• ARA-C
• DAUNORUBICIN
• MTS ASSAY