Korean J Hematol 2001; 36(2):

Published online June 30, 2001

© The Korean Society of Hematology

급성골수성백혈병 환자에서 약제내성유전자의 발현과 임상적 약제 감수성과의 관계

김기원, 박석영, 김희정

가톨릭대학교 의과대학 내과학교실,
가톨릭대학교 의과대학 임상병리과학교실

The Relationship between Clinical Drug Sensitivity and Expression of Drug Resistance Genes in Patients with Acute Myelogenous Leukemia

Kee Won Kim, Suk Young Park, Hee Jung Kim

Department of Internal Medicine, Clinical Pathology College of Medicine, The Catholic University of Korea, Seoul, Korea

Abstract

Background : The occurrence of drug resistance (DR) is one of the obstacles in the successful chemotherapeutic treatment of cancer. Multidrug resistance-1 (MDR-1), multidrug resistance associated protein (MRP), topoisomerase IIα (Topo IIα) and cytidine deaminase (CDA) have been reported to be genes associated with DR in acute myelogenous leukemia (AML). But the relationship between drug sensitivity and expression of DR genes in AML has not been well defined. We investigated the expression of
those DR genes in AML, at diagnosis and in relapse, with the assessment of clinical response.
Methods :
Leukemic cells isolated from bone marrow of 20 patients with AML [complete remission (CR); 10, non-CR; 10] and 10 patients with non-malignant hematological diseases as control. The expression level of DR genes was determined by
reverse transcription polymerase chain reaction (RT-PCR) and assessed semiquantitatively as the optical density ratio of PCR product of the target gene to that of β2-microglobulin (β2-MG).
Results :
The results are as follows.
1) The expression of DR genes was not different between CR and control group.
2) The expressions of MDR-1 and MRP in non-CR group were significantly higher than those of CR and control group (P<0.05), but there were no differences in Topo IIα and CDA.
3) In several relapsed cases after CR, the expressions of all of those DR genes in relapse were much increased as compared with those at diagnosis.
Conclusion :
RT-PCR and semiquantitative assessment of DR genes in AML shows that the increased expression of MDR-1 and MRP is a poor prognostic factor in the chemotherapy of AML. The development of effective strategy to suppress the
increased expression of those genes, especially in relapsed AML, should be required.

Keywords Acute myelogenous leukemia, Drug resistance, Chemotherapy

Article

Korean J Hematol 2001; 36(2): 115-122

Published online June 30, 2001

Copyright © The Korean Society of Hematology.

급성골수성백혈병 환자에서 약제내성유전자의 발현과 임상적 약제 감수성과의 관계

김기원, 박석영, 김희정

가톨릭대학교 의과대학 내과학교실,
가톨릭대학교 의과대학 임상병리과학교실

The Relationship between Clinical Drug Sensitivity and Expression of Drug Resistance Genes in Patients with Acute Myelogenous Leukemia

Kee Won Kim, Suk Young Park, Hee Jung Kim

Department of Internal Medicine, Clinical Pathology College of Medicine, The Catholic University of Korea, Seoul, Korea

Abstract

Background : The occurrence of drug resistance (DR) is one of the obstacles in the successful chemotherapeutic treatment of cancer. Multidrug resistance-1 (MDR-1), multidrug resistance associated protein (MRP), topoisomerase IIα (Topo IIα) and cytidine deaminase (CDA) have been reported to be genes associated with DR in acute myelogenous leukemia (AML). But the relationship between drug sensitivity and expression of DR genes in AML has not been well defined. We investigated the expression of
those DR genes in AML, at diagnosis and in relapse, with the assessment of clinical response.
Methods :
Leukemic cells isolated from bone marrow of 20 patients with AML [complete remission (CR); 10, non-CR; 10] and 10 patients with non-malignant hematological diseases as control. The expression level of DR genes was determined by
reverse transcription polymerase chain reaction (RT-PCR) and assessed semiquantitatively as the optical density ratio of PCR product of the target gene to that of β2-microglobulin (β2-MG).
Results :
The results are as follows.
1) The expression of DR genes was not different between CR and control group.
2) The expressions of MDR-1 and MRP in non-CR group were significantly higher than those of CR and control group (P<0.05), but there were no differences in Topo IIα and CDA.
3) In several relapsed cases after CR, the expressions of all of those DR genes in relapse were much increased as compared with those at diagnosis.
Conclusion :
RT-PCR and semiquantitative assessment of DR genes in AML shows that the increased expression of MDR-1 and MRP is a poor prognostic factor in the chemotherapy of AML. The development of effective strategy to suppress the
increased expression of those genes, especially in relapsed AML, should be required.

Keywords: Acute myelogenous leukemia, Drug resistance, Chemotherapy

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