Predictive value for treatment outcome in acute myeloid leukemia of cellular daunorubicin accumulation and P-glycoprotein expression simultaneously determined by flow cytometry.
Fiche publication
Date publication
avril 1995
Journal
Blood
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GUERCI-BRESLER Agnès, Pr MERLIN Jean-Louis
Tous les auteurs :
Guerci A, Merlin JL, Missoum N, Feldmann L, Marchal S, Witz F, Rose C, Guerci O
Lien Pubmed
Résumé
To evaluate the clinical relevance of multidrug resistance (MDR) phenotype, the intracellular daunorubicin accumulation (IDA) and P-glycoprotein (P-gp) expression were investigated in 87 adult patients with acute leukemia: 69 patients with de novo acute myeloid leukemia (AML), 10 with AML at relapse, and eight with secondary leukemia to myelodysplastic syndromes (MDS-AML). IDA and P-gp expression were determined by double-labeling flow cytometry analysis. Of 87 patients, 36 expressed P-gp (41%). P-gp expression was more frequently observed in AML at relapse and MDS-AML as compared with de novo AML (P = .0001). P-gp expression was significantly associated with CD34 expression (P = .0003) and chromosome 7 abnormalities (P = .027). A significantly reduced IDA was observed in P-gp+ as compared with P-gp- patients (P = .0007). Of the 87 patients, 51 achieved complete remission (CR). A reduced IDA was observed in patients in failure as compared with patients in CR (22% +/- 17% v 42% +/- 21%; P = 10(-4). Twelve of 36 P-gp+ patients as compared with 40 of 51 P-gp- patients achieved CR (33% v 78%; P = 10(-4). The prognostic value of IDA and P-gp expression was confirmed in multivariate analysis. These data suggest that the determination of IDA and P-gp expression may be useful in designing therapy for patients with AML.
Mots clés
Acute Disease, Adolescent, Adult, Aged, Antigens, CD, analysis, Antigens, CD34, Antineoplastic Combined Chemotherapy Protocols, therapeutic use, Blast Crisis, blood, Blood Cell Count, Bone Marrow, chemistry, Chromosome Deletion, Chromosomes, Human, Pair 7, ultrastructure, Cytarabine, administration & dosage, Daunorubicin, administration & dosage, Drug Resistance, Multiple, Female, Flow Cytometry, Gene Expression, Humans, Idarubicin, administration & dosage, Karyotyping, Leukemia, Myeloid, blood, Male, Middle Aged, Mitoxantrone, administration & dosage, Monosomy, Myelodysplastic Syndromes, pathology, Neoplasm Proteins, analysis, Neoplasm Recurrence, Local, Neoplastic Stem Cells, chemistry, P-Glycoprotein, analysis, Prognosis, Prospective Studies, Quinine, administration & dosage, Remission Induction, Risk, Salvage Therapy, Treatment Outcome
Référence
Blood. 1995 Apr;85(8):2147-53