Antibody Binding Capacity for Evaluation of MDR-Related Proteins in Acute Promyclocytic Leukemia: Onset Versus Relapse Expression

Daniela Damiani, Mariagrazia Michieli, Angela Michelutti, Anna Candoni, Raffaella Stocchi, Paola Masolini, Antonella Geromin, Teresa Michelutti, Donatella Raspadori, Micaela Ippoliti, Francesco Lauria, Renato Fanin

Research output: Contribution to journalArticle

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Abstract

Background: Multidrug resistance (MDR) remains a major obstacle for successful treatment in cancer, in particular in acute leukemia. In acute promyelocytic leukemia (APL), the high sensitivity to anthracyclines appears to be attributable to the low frequency of MDR proteins overexpression at onset even if 30% of patients still relapse and become resistant to therapy. In attempt to explain different blast cell sensitivity, we studied the expression of PGP, MRP1, MRP2, and LRP in 45 cases of APL, comparing onset of disease with relapse. Methods: PGP, LRP, and MRP on bone marrow or peripheral blood blast cells were evaluated by flow cytometry using the MRK-16, LRP-56, MRP-m6, and MRP2 antibodies and results expressed by the mean fluorescence index (MFI). The antibody binding capacity (ABC) for each MDR protein was also calculated. Results: At diagnosis, only 2 of 45 patients overexpressed PGP and 1 overexpressed LRP. PGP and LRP overexpressing cases significantly grew up during disease progression and at second relapse mean PGP MF1 and mean LRP MF1 were significantly higher than at onset (P = 0.001 and P = 0.008, respectively). By analyzing ABC, the same trend was more evident because a significant increment of PGP and LRP was observed at second (P = 0.002 and P = 0.002, respectively), but even at first relapse (P = 0.018 and P = 0.002, respectively). No changes were demonstrated in MRP1 and MRP2 expression in any phase of disease considered. Conclusions: Our data confirm the low expression at diagnosis of proteins related to development of drug resistance in APL. The evidence of a relative easy induction of PGP and LRP, but not of MRP, can be useful in choosing drugs to employ for consolidation or rescue therapy.

Original languageEnglish
Pages (from-to)40-45
Number of pages6
JournalCytometry Part B - Clinical Cytometry
Volume59
Issue number1
Publication statusPublished - May 2004

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P-Glycoproteins
Acute Promyelocytic Leukemia
Leukemia
Recurrence
Antibodies
Anthracyclines
Multiple Drug Resistance
Drug Resistance
Disease Progression
Blood Cells
Flow Cytometry
Therapeutics
Fluorescence
Bone Marrow
Pharmaceutical Preparations
Neoplasms
Proteins

Keywords

  • Acute promyelocytic leukemia
  • Multidrug resistance-related protein
  • Rescue therapy

ASJC Scopus subject areas

  • Hematology
  • Cell Biology
  • Pathology and Forensic Medicine
  • Biophysics
  • Endocrinology

Cite this

Antibody Binding Capacity for Evaluation of MDR-Related Proteins in Acute Promyclocytic Leukemia : Onset Versus Relapse Expression. / Damiani, Daniela; Michieli, Mariagrazia; Michelutti, Angela; Candoni, Anna; Stocchi, Raffaella; Masolini, Paola; Geromin, Antonella; Michelutti, Teresa; Raspadori, Donatella; Ippoliti, Micaela; Lauria, Francesco; Fanin, Renato.

In: Cytometry Part B - Clinical Cytometry, Vol. 59, No. 1, 05.2004, p. 40-45.

Research output: Contribution to journalArticle

Damiani, D, Michieli, M, Michelutti, A, Candoni, A, Stocchi, R, Masolini, P, Geromin, A, Michelutti, T, Raspadori, D, Ippoliti, M, Lauria, F & Fanin, R 2004, 'Antibody Binding Capacity for Evaluation of MDR-Related Proteins in Acute Promyclocytic Leukemia: Onset Versus Relapse Expression', Cytometry Part B - Clinical Cytometry, vol. 59, no. 1, pp. 40-45.
Damiani, Daniela ; Michieli, Mariagrazia ; Michelutti, Angela ; Candoni, Anna ; Stocchi, Raffaella ; Masolini, Paola ; Geromin, Antonella ; Michelutti, Teresa ; Raspadori, Donatella ; Ippoliti, Micaela ; Lauria, Francesco ; Fanin, Renato. / Antibody Binding Capacity for Evaluation of MDR-Related Proteins in Acute Promyclocytic Leukemia : Onset Versus Relapse Expression. In: Cytometry Part B - Clinical Cytometry. 2004 ; Vol. 59, No. 1. pp. 40-45.
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AU - Damiani, Daniela

AU - Michieli, Mariagrazia

AU - Michelutti, Angela

AU - Candoni, Anna

AU - Stocchi, Raffaella

AU - Masolini, Paola

AU - Geromin, Antonella

AU - Michelutti, Teresa

AU - Raspadori, Donatella

AU - Ippoliti, Micaela

AU - Lauria, Francesco

AU - Fanin, Renato

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