Prognostic Implication of MDR1 (Multidrug Resistance) Gene Expression in Childhood Acute Leukemia / 대한혈액학회지

ABSTRACT

BACKGROUND: The most important mechanism of drug resistance is related to the over-expression of P-glycoprotein which is encoded by the MDR1 gene. The expression of MDR1 and its clinical implication in childhood leukemias has not been extensively assessed. METHODS: To evaluate the expression of MDR1 gene and its prognostic implication on the remission induction rate, relapse rate and survival, we assayed mdr1 mRNA by reverse-transcriptase polymerase chain reaction (RT-PCR) from bone marrow samples of 23 childhood ALL and 17 AML patients. The prognostic factors were analyzed by logistic regression and Cox proportional hazards model. RESULTS: mdr1 mRNA was expressed in 51.5% of patients at diagnosis. MDR1 status did not influence the remission induction rate both in ALL and AML. The relapse rate was significantly higher in MDR1 positive patients than in negative patients (29.4% vs. 0.0%, p=0.04). The cumulative relapse probability at 2 year was 60% vs 0% according to MDR1 status (p=0.006), suggesting the importance of MDR1 in the mechanism of relapse for childhood leukemias. The Kaplan-Meier 3-yr event-free survival (EFS) was 42.7% for MDR1 positive group, and 93.8% for negative patients (p=0.046). Analyses of prognostic factors showed that mdr1 mRNA expression was the sole prognostic factor predicting the poor EFS(X 2, 6.217; p=0.013). CONCLUSION: These results suggest that RT-PCR for mdr1 mRNA expression is a readily feasible and useful method of assessing multidrug resistance. The expression of MDR1 was found to be the most important prognostic factor predicting the possibility of relapse and EFS in patients with childhood leukemia.