P-glycoprotein, lung resistance-related protein and multidrug resistance-associated protein in de novo adult acute lymphoblastic leukaemia

Daniela Damiani, Angela Michelutti, Mariagrazia Michieli, Paola Masolini, Raffaella Stocchi, Antonella Geromin, Anna Ermacora, Domenico Russo, Renato Fanin, Michele Baccarani

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)519-527
Number of pages9
JournalBritish Journal of Haematology
Volume116
Issue number3
DOIs
Publication statusPublished - 2002

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Multidrug Resistance-Associated Proteins
P-Glycoprotein
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Daunorubicin
P-Glycoproteins
Disease-Free Survival
Proteins
Multiple Drug Resistance
major vault protein
Flow Cytometry
Recurrence
Therapeutics

Keywords

  • Adult acute lymphoblastic leukaemia
  • Lung resistance-related protein
  • Multidrug resistance-associated protein
  • P-glycoprotein

ASJC Scopus subject areas

  • Hematology

Cite this

P-glycoprotein, lung resistance-related protein and multidrug resistance-associated protein in de novo adult acute lymphoblastic leukaemia. / Damiani, Daniela; Michelutti, Angela; Michieli, Mariagrazia; Masolini, Paola; Stocchi, Raffaella; Geromin, Antonella; Ermacora, Anna; Russo, Domenico; Fanin, Renato; Baccarani, Michele.

In: British Journal of Haematology, Vol. 116, No. 3, 2002, p. 519-527.

Research output: Contribution to journalArticle

Damiani, D, Michelutti, A, Michieli, M, Masolini, P, Stocchi, R, Geromin, A, Ermacora, A, Russo, D, Fanin, R & Baccarani, M 2002, 'P-glycoprotein, lung resistance-related protein and multidrug resistance-associated protein in de novo adult acute lymphoblastic leukaemia', British Journal of Haematology, vol. 116, no. 3, pp. 519-527. https://doi.org/10.1046/j.0007-1048.2001.03322.x
Damiani, Daniela ; Michelutti, Angela ; Michieli, Mariagrazia ; Masolini, Paola ; Stocchi, Raffaella ; Geromin, Antonella ; Ermacora, Anna ; Russo, Domenico ; Fanin, Renato ; Baccarani, Michele. / P-glycoprotein, lung resistance-related protein and multidrug resistance-associated protein in de novo adult acute lymphoblastic leukaemia. In: British Journal of Haematology. 2002 ; Vol. 116, No. 3. pp. 519-527.
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abstract = "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.",
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AU - Michelutti, Angela

AU - Michieli, Mariagrazia

AU - Masolini, Paola

AU - Stocchi, Raffaella

AU - Geromin, Antonella

AU - Ermacora, Anna

AU - Russo, Domenico

AU - Fanin, Renato

AU - Baccarani, Michele

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