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P‐glycoprotein, lung resistance‐related protein and multidrug resistance‐associated protein in de novo adult acute lymphoblastic leukaemia
Author(s) -
Damiani Daniela,
Michelutti Angela,
Michieli Mariagrazia,
Masolini Paola,
Stocchi Raffaella,
Geromin Antonella,
Ermacora Anna,
Russo Domenico,
Fanin Renato,
Baccarani Michele
Publication year - 2002
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.0007-1048.2001.03322.x
Subject(s) - daunorubicin , multiple drug resistance , medicine , p glycoprotein , flow cytometry , immunology , gastroenterology , chemotherapy , drug resistance , biology , microbiology and biotechnology
Summary. P‐glycoprotein (P‐gp), lung resistance‐related protein (LRP) and multidrug resistance‐associated protein (MRP) expression, and blast cell intracellular daunorubicin accumulation (IDA) were evaluated in 95 previously untreated cases of adult acute lymphoblastic leukaemia (ALL) using flow cytometry. Forty‐five out of 95 (47%) patients were P‐gp positive (+), 12/66 (18%) were LRP+ and 11/66 (17%) were MRP+. Eighteen out of 66 (28%) patients showed a simultaneous multidrug resistance (MDR)‐related protein expression higher than controls for more than one protein, while 24/66 (36%) cases did not overexpress any protein. Twenty‐one out of 24 (87%) cases overexpressing at least one MDR‐related protein had a defect in accumulating daunorubicin into their blast cells, while only 4/24 (16%) cases who did not overexpress any protein had similar features. The complete remission rates were similar in MDR‐positive and ‐negative (–) patients but relapses within 6 months were more frequent in P‐gp+ cases, and therefore the disease‐free survival duration was shorter in P‐gp+ than in P‐gp– patients ( P = 0·01). The number of MRP+ and/or LRP+ cases was too small to be able to draw any conclusion on their role in affecting or predicting therapy outcome. In conclusion, P‐gp overexpression associated with a defect in daunorubicin accumulation is a frequent feature in adult ALL at onset and seems to be related to poorer therapy outcome and, consequently, a shorter disease‐free survival. LRP and MRP overexpression seems to be a rare event and no conclusion can be drawn on its prognostic role.