Decreased activity of the multidrug resistance P-glycoprotein in acquired aplastic anaemia: Possible pathophysiologic implications

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Abstract

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.

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Calado, R. T., Garcia, A. B., & Falcão, R. P. (1998). Decreased activity of the multidrug resistance P-glycoprotein in acquired aplastic anaemia: Possible pathophysiologic implications. British Journal of Haematology, 102(5), 1157–1161. https://doi.org/10.1046/j.1365-2141.1998.00882.x

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