C3435T Polymorphism of MDR1 Gene Is Not Associated with p-Glycoprotein Function of Leukemic Blasts and Clinical Outcomes in Patients with Acute Myeloid Leukemia.

P-glycoprotein (P-gp) function of leukemic blasts is associated with chemotherapy resistance in acute myeloid leukemia (AML). The C3435T polymorphism in the human MDR1 gene has been studied in AML and contradictory results were reported regarding clinical implications of the polymorphism. We investigated the association of C3435T polymorphism of MDR1 gene with P-gp function of leukemic blasts and clinical outcomes in patients with AML excluding M3 subtype. A total of 200 patients, 127 males and 73 females, were included in this study. Median age was 44 years (range, 14–75). All patients were newly diagnosed and were treated with standard ‘7+3’ induction chemotherapy regimens at the Asan Medical Center, Seoul, Korea between May 1999 and November 2006. The C3435T polymorphism was analyzed with PCR/RFLP method. P-gp function of leukemic blasts was measured at diagnosis by the rhodamine-123 efflux assay. The clinico-laboratory data at diagnosis and data on clinical outcomes were obtained from the AMC Leukemia Registry. Genotype frequency of C3435T polymorphism was 71 (35.5%) for CC, 93 (46.5%) for CT, and 36 (18.0%) for TT. There were no significant differences between different genotypes of C3435T polymorphism regarding age, sex, FAB subtypes, initial leukocyte counts, percentages of blasts in bone marrow or blood at diagnosis, and cytogenetic risk groups. P-gp function of leukemic blasts was not significantly different according to the genotype of C3435T polymorphism: 32.2 ± 24.0% for CC, 35.8 ± 21.4% for CT, and 29.1 ± 24.0% for TT (P=0.370). Complete remission was induced in 79.2% for CC, 79.8% for CT, and 77.8% for TT (P=0.969). Overall, relapse-free and event-free survival probabilities at 5 years were 47.6%, 55.4% and 51.0% for CC, 51.3%, 51.0% and 42.5% for CT, and 53.1%, 60.0% and 55.0% for TT (P= 0.594, 0.932 and 0.764, respectively). In conclusion, C3435T polymorphism does not have significant clinical implications in AML regarding P-gp function of leukemic blasts and clinical outcomes.