Evaluation of multidrug resistance in acute leukemia using real-time polymerase chain reaction

Background: Despite the advances in the cure rate for acute leukemia, ~25% of affected patients develop relapses. Expression of genes for the multidrug resistance (MDR1) and breast cancer-resistance protein (BCRP) may confer the phenotype of resistance to the treatment of acute leukemia. Objective: To analyze the expression of the MDR1 and BCRP genes in new cases of acute leukemia using real-time PCR (RT-PCR) and to determine the correlation between their expression and overall survival (OS). Patients and methods: Patients diagnosed with acute myeloblastic leukemia (AML) (n = 15) and acute lymphoblastic leukemia (ALL) (n = 35), and 20 blood donors as a control group were included in this study. The expressions of mRNA for the MDR1 and BCRP genes were assessed by RT-PCR. Myeloid surface markers such as CD34, CD33, CD13, and CD14 and lymphoid surface markers such as CD3, CD5, CD2, CD4, CD8, and CD19 were analyzed using flow cytometry. Results: The groups with the MDR gene and the BCRP gene showed a highly significant difference compared with the control group (P 0.000). The relation between MDR and BCRP in both AML and ALL groups showed no significant difference. There was a significant difference between BCRP expression in the AML and ALL groups (P 0.01). There was no significant difference in the OS between MDR+ cases and MDR- cases in the AML and ALL groups. In contrast, the OS in BCRP+ cases and BCRP- cases showed a significant difference between AML and ALL groups (P 0.01). No significant difference was detected between OS in AML (MDR+, CD34+) and AML (MDR+, CD34−). In contrast, OS between AML (BCRP+, CD34+) and AML (BCRP+, CD34−) showed a significant difference (P 0.01). The difference between OS in ALL (MDR+, CD34+) and ALL (MDR+, CD34−) was not significant. In contrast, a significant difference was detected between OS in ALL (BCRP+, CD34+) and ALL (BCRP+, CD34−) (P 0.01). OS in the AML group that was BCRP+ (CD13+) showed a significant difference (P 0.01). In the ALL group, the association between MDR+ and CD19+ or BCRP+ and CD19+ did not affect the survival significantly. Conclusion: We concluded that the evaluation of the expression of genes for resistance to antineoplastic drugs in acute leukemia upon diagnosis, and particularly the expression of the BCRP gene, may be of clinical relevance.