Frequent expression of MDR1 and MDR3 genes in acute myelocytic leukemia cells with t(8;21) (q22;q22)

Multidrug resistance (MDR) 1 and MDR3 gene expression were examined in acute myelocytic leukemia (AML) cells from 126 Japanese patients. In 119 AML patients at diagnosis 52 were revealed to have P-gp/MDR1 (43.7%). AML cases with t(8;21) had a higher incidence of P-gp expression (13/17; 76.5%) than cases with other karyotypes (33/89; 37.1%) (p=0.0062). CD19(+) cases expressed P-gp frequently (17/25) as did CD7(+) cases (24/35). In 17 CD19(+) AML with P-gp expression, 12 had t(8;21) abnormality. In 68 AML samples examined, MDR3 mRNA was detected in 11 cases, 9 of which had the t(8;21) abnormality. The MDR3(+) t(8;21) AML samples were also positive for CD19. We analyzed P-gp expression at both diagnosis and relapse in 18 AML patients. All 11 P-gp(+) cases at relapse, in which 5 patients were P-gp negative at diagnosis, showed either t(8;21) or CD7 positivity. Our data demonstrated that expression of MDR1 and MDR3 in AML is closely associated with chromosome abnormality t(8;21) and expression of immature lymphoid antigen CD19 as well as CD7. Kasumi-1, a t(8;21) AML cell line, was demonstrated to lose P-gp by the treatment of 1,25(OH)(2)D-3, a monocyte/macropharge differentiation inducer, suggesting the possible contribution to the therapy for AML.