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

Kim, Kee Won; Kim, Hee Jung; Park, Suk Young

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 IIalpha (Topo IIalpha) 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 as sessed semiquantitatively as the optical density ratio of PCR product of the target gene to that of beta2-microglobulin (beta2-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 IIalpha 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.