Expression of Multidrug Resistance Genes, mdr1, mrp, Topo IIalpha and Topo IIbeta in Childhood Acute Lymphoblastic Leukemia / 대한소아혈액종양학회지

ABSTRACT

PURPOSE: Multidrug resistance in the treatment of cancer mediated by several drug resistant genes impedes the successful management of cancer. The authors investigated the expression of drug resistant genes, including multidrug resistance (mdr1), multidrug resistance-associated protein (mrp), topoisomerase IIalpha (Topo IIalpha), and topoisomerase IIbeta (Topo IIbeta) in patients with childhood acute lymphoblastic leukemia (ALL; n=24) and in normal controls (n=6). METHODS: The levels of their transcripts in the bone marrow mononuclear cells were compared by semiquantitative RT-PCR, comparing the optical density ratio of PCR products of target genes to that of beta2-microglobulin. RESULTS: The expression of all 4 genes were detected in ALL patients as well as in normal controls except for Topo IIalpha, which were not detected in controls. The expression levels of mdr1, mrp and Topo IIbeta in ALL patients were significantly higher than those of normal controls [(2.1+/-2.2 vs 0.9+/-0.3, P> 0.024), (0.5+/-0.2 vs 0.2+/-0.1, P=0.016), and (0.7+/-0.2 vs 0.3+/-0.1, P=0.016)], respectively. The expression level of mdr1 gene transcript was relatively higher than those of mrp and Topo IIbeta. However, there was no correlation between the expression of multidrug resistant genes and survival and/or relapse of ALL. CONCLUSION: Though multidrug resistance genes did not serve as an independent prognostic factor, they might be used for markers for disease progression or relapse in childhood ALL. A longitudinal study of those genes is necessary to elucidate the prognostic significance in childhood ALL.