Korean J Lab Med.  2003 Jun;23(3):143-150.

Relation among the Tests and Comparison of Positivity of Tests for Multi-Drug Resistance in Newly Diagnosed Acute Leukemia

• Lee NY
• Bae HG
• Kwon EH
• Heo WB
• Shin SH
• Suh JS

Abstract

BACKGROUND
The expression of multi-drug resistance (MDR) in acute leukemia was known to decrease the outcome of chemotherapy and to increase the rate of relapse. Of the mechanism of MDR, the most well known is P-glycoprotein (P-gp) encoded by the mdr1 gene. There are MDR genes, P-gp tests and drug efflux function tests for the clinical measurement of MDR. To assess the clinical usefulness and MDR expression status in acute leukemia, MDR tests were performed. METHODS: MDR expression was assessed by MDR1 mRNA RT-PCR and flow cytometry measuring P-gp and daunorubicin (DNR) efflux in 77 patients with newly diagnosed acute leukemia (AL) including 48 acute myeloid leukemia (AML), 16 acute lymphoblastic leukemia (ALL) and 13 acute mixed-lineage leukemia (AMLL). The CD34 surface-marker study was also done by flow cytometry. The result of chemotherapy was evaluated by the percentage of remnant bone marrow (BM) blasts. RESULTS: The positivity of MDR1 mRNA was 57.1% (44/77) in AL, 61.5% (8/13) in AMLL, 60.4% (29/48) in AML, and 43.8% (7/16) in ALL. The positivity of P-gp expression was 36.5% (27/74) in AL and 100% in AML. The positivity of the DNR efflux test was 30.1% (22/73) in AL, 40.0% (18/45) in AML, 23.1% (3/13) in AMLL, and 6.7% (1/15) in ALL. There was a significant correlation between MDR1 mRNA and P-gp expression and between MDR1 mRNA and CD34 expression in AML. There was a significant correlation between the percentages of residual blast cells in BM and P-gp expression (P=0.039, r=0.312). CONCLUSIONS: It can be clinically useful to perform the mdr1 gene and P-gp test simultaneously both in newly diagnosed acute leukemia patients. The effectiveness of tests for MDR can be helpful to predict the outcome of chemotherapy.

Keyword

Multi-drug resistance; Acute leukemia; P-glycoprotein; mdr1 gene; Daunorubicin efflux

MeSH Terms

Bone Marrow
Daunorubicin
Drug Resistance, Multiple*
Drug Therapy
Flow Cytometry
Genes, MDR
Humans
Leukemia*
Leukemia, Myeloid, Acute
P-Glycoprotein
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Recurrence
RNA, Messenger
Daunorubicin
P-Glycoprotein
RNA, Messenger