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Decreased activity of the multidrug resistance P‐glycoprotein in acquired aplastic anaemia: possible pathophysiologic implications
Author(s) -
Calado Rodrigo T.,
Garcia Aglair B.,
FalcÃO Roberto P.
Publication year - 1998
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1998.00882.x
Subject(s) - p glycoprotein , efflux , pathophysiology , daunorubicin , immunology , rhodamine 123 , multiple drug resistance , medicine , biology , drug resistance , leukemia , microbiology and biotechnology , genetics
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.