Decreased activity of the multidrug resistance P-glycoprotein in acquired aplastic anaemia: possible pathophysiologic implications.
To address a possible impairment of multidrug resistance mechanisms in acquired aplastic anaemia (AA), the functions of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) were respectively assessed by rhodamine 123 (Rh123) and daunorubicin (DNR) efflux in peripheral blood lymphocytes from AA patients. The proportion of Rh123-effluxing T cells was significantly decreased in AA, relative to controls. Interestingly, these changes were also present in patients with AA in remission. Conversely, Rh123 efflux in B and natural killer (NK) cells and DNR efflux in peripheral blood lymphocytes were unchanged. These data indicated that P-gp activity was decreased in AA not only during the development of the disease, but also after remission, introducing a new concept on the pathophysiology of AA by suggesting that it may contribute to drug-induced injury to haemopoietic cells in some cases of AA, by increasing the proportion of susceptible cells.
Calado
R T
RT
Department of Clinical Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Garcia
A B
AB
Falcão
R P
RP
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000139:chemically induced / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000378:metabolism; D018432:Drug Resistance, Multiple; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D008297:Male; D020112:Rhodamine 123 / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005456:Fluorescent Dyes; D020112:Rhodamine 123; D003630:Daunorubicin