The expression of P-glycoprotein (P-gp), encoded by the MDR1 gene, is an
independent adverse prognostic factor for response and survival in de novo
acute myeloid leukemia (AML). Little is known about MDR1 expression during
the development of disease. The present study investigated whether MDR1
gene- related clonal selection occurs in the development from diagnosis to
relapsed AML, using a genetic polymorphism of the MDR1 gene at position
2677. Expression and function of P-gp were studied using monoclonal
antibodies MRK16 and UIC2 and the Rhodamine 123 retention assay with or
without PSC 833. No difference was found in the levels of P-gp function
and expression between diagnosis and relapse in purified paired blast
samples from 30 patients with AML. Thirteen patients were homozygous for
the genetic polymorphism of MDR1 (n = 7 for guanine, n = 6 for thymidine),
whereas 17 patients were heterozygous (GT). In the heterozygous patients,
no selective loss of one allele was observed at relapse. Homozygosity for
the MDR1 gene (GG or TT) was associated with shorter relapse-free
intervals (P =.002) and poor survival rates (P =.02), compared with
heterozygous patients. No difference was found in P-gp expression or
function in patients with AML with either of the allelic variants of the
MDR1 gene. It was concluded that P-gp function or expression is not
upregulated at relapse/refractory disease and expression of one of the
allelic variants is not associated with altered P-gp expression or
function in AML, consistent with the fact that MDR1 gene-related clonal
selection does not occur when AML evolves to recurrent disease. (Blood.
2001;97:3605-3611
