Expression of multidrug resistance (MDR) proteins and in vitro drug resistance in acute leukemias.
The expression of the multidrug 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-sulfophenyl)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.
Fazlina
N
N
Department of Pathology, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Maha
A
A
Jamal
R
R
Zarina
A L
AL
Cheong
S K
SK
Hamidah
H
H
Ainoon
O
O
Zulkifli
S Z
SZ
Hamidah
N H
NH
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002470:Cell Survival; D002648:Child; D002675:Child, Preschool; D004396:Coloring Agents / Q000032:analysis; D003561:Cytarabine / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007223:Infant; D020128:Inhibitory Concentration 50; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism*; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008773:Methylphenazonium Methosulfate / Q000494:pharmacology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism; D012008:Recurrence; D013194:Staining and Labeling / Q000379:methods; D013778:Tetrazolium Salts / Q000032:analysis; D013844:Thiazoles / Q000032:analysis; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000648:ultrastructure
D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D004396:Coloring Agents; D009363:Neoplasm Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D003561:Cytarabine; C070380:3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; D008773:Methylphenazonium Methosulfate; D003630:Daunorubicin