J Korean Med Sci.  2006 Apr;21(2):253-258. 10.3346/jkms.2006.21.2.253.

Prognostic Significance of Multidrug Resistance Gene 1 (MDR1), Multidrug Resistance-related Protein (MRP) and Lung Resistance Protein (LRP) mRNA Expression in Acute Leukemia

• Huh HJ
• Park CJ
• Jang S
• Seo EJ
• Chi HS
• Lee JH
• Lee KH
• Seo JJ
• Moon HN
• Ghim T

• KMID: 1781831
• DOI: http://doi.org/10.3346/jkms.2006.21.2.253

Abstract

The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (39 myeloid, 32 lymphoblastic) using nested RT-PCR. The expression of each of these genes was then expressed as a ratio in relation to beta-actin gene expression, and the three genes were categorized as being either 0, 1+, 2+ or 3+. MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1% and 45.1 %, respectively. LRP mRNA expression was significantly associated with resistance to induction chemotherapy in acute leukemia patients, and in the AML proportion (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression was associated with poorer 2-yr survival (p=0.049 and p=0.04, respectively). Patients expressing both MRP and LRP mRNA had poorer outcomes and had worse 2-yr survival. The present data suggest that MDR expression affects complete remission and survival rates in acute leukemia patients. Thus, determination of MDR gene expression at diagnosis appears likely to provide useful prognostic information for acute leukemia patients.

Keyword

Genes, MDR; Multidrug Resistance Gene 1; P-Glycoprotein Multidrug Resistance-related Protein 1; lung resistance protein; Prognosis; Leukemia

MeSH Terms

Vault Ribonucleoprotein Particles/*genetics
Survival Rate
RNA, Neoplasm/genetics
RNA, Messenger/genetics
Prognosis
Neoplasm Proteins/*genetics
Multidrug Resistance-Associated Proteins/*genetics
Middle Aged
Male
Leukemia, Myelocytic, Acute/drug therapy/genetics/mortality
Leukemia, Lymphocytic, Acute/drug therapy/genetics/mortality
Leukemia/drug therapy/*genetics/mortality
Infant
Humans
*Genes, MDR
Gene Expression
Female
Child, Preschool
Child
Base Sequence
Aged
Adult
Adolescent

Figure

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  Fig. 1 RT-PCR products following MDR1, MRP and LRP mRNA amplification. Lane S, size marker; lane 1, MDR1-positive cell line (band at 243 bp); lane 2, DW; lane 3, normal bone marrow; lane 4, MDR1-positive patient; lane 5, MRP-positive line (bands at 575 and 420 bp); lane 6, DW; lane 7, normal bone marrow; lane 8, s-positive patient; lane 9, LRP-positive cell line (band at 239 bp); lane 10, DW; lane 11, normal bone marrow; lane 12, LRP-positive patient; lane 13, β-actin (internal control, band at l66 bp). (DW=deionized water (negative control)).

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  Fig. 2 Relationship between MRP mRNA expression and 2-yr survival in acute leukemia patients.

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  Fig. 3 Relationship between MDR1 mRNA expression levels and 2-yr survival in acute leukemia patients.

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