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=0.006 2). CD19(+) cases expressed P-gp frequently (17/25) as did CD7(+) case s (24/35). In 17 CD19(+) AML with P-gp expression, 12 had t(8;21) abno rmality. In 68 AML samples examined, MDR3 mRNA was detected in 11 case s, 9 of which had the t(8;21) abnormality. The MDR3(+) t(8;21) AML sam ples 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 rela pse, in which 5 patients were P-gp negative at diagnosis, showed eithe r 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 C D7. Kasumi-1, a t(8;21) AML cell line, was demonstrated to lose P-gp b y the treatment of 1,25(OH)(2)D-3, a monocyte/macropharge differentiat ion inducer, suggesting the possible contribution to the therapy for A ML.