Korean J Hematol 1998; 33(3):
Published online September 30, 1998
© The Korean Society of Hematology
소아 급성 백혈병 환자에서 다제약제 내성유전자 (MDR1)의 발현이 재발 및 생존에 미치는 영향
국훈, 김준희, 김찬종, 박지영, 조창이, 조성호, 나정아, 황태주
전남대학교 의과대학 소아과학교실, 전남대학교 의과학 연구소,
전남대학교병원 임상연구소
Prognostic Implication of MDR1 (Multidrug Resistance) Gene Expression in Childhood Acute Leukemia
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.
Keywords Multidrug resistance; RT-PCR; Acute Leukemia; Childhood; Prognostic factor; Relapse; Survival;
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Korean J Hematol 1998; 33(3): 334-352
Published online September 30, 1998
Copyright © The Korean Society of Hematology.
소아 급성 백혈병 환자에서 다제약제 내성유전자 (MDR1)의 발현이 재발 및 생존에 미치는 영향
국훈, 김준희, 김찬종, 박지영, 조창이, 조성호, 나정아, 황태주
전남대학교 의과대학 소아과학교실, 전남대학교 의과학 연구소,
전남대학교병원 임상연구소
Prognostic Implication of MDR1 (Multidrug Resistance) Gene Expression in Childhood Acute Leukemia
Hoon Kook, Jun Hee Kim, Chan Jong Kim, Ji Young Park, Chang Yee Cho, Sung Ho Cho, Jung Ah Na, Tai Ju Hwang
Department of Pediatrics, The Research Institute of Medical Sciences,
The Research Institute of Clinical Medicine, Chonnam University Medical School, Kwangju, Korea
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.
Keywords: Multidrug resistance, RT-PCR, Acute Leukemia, Childhood, Prognostic factor, Relapse, Survival,
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