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Titolo:
Heterogeneity of isolated mononuclear cells from patients with acute myeloid leukemia affects cellular accumulation and efflux of daunorubicin
Autore:
Knaust, E; Porwit-MacDonald, A; Gruber, A; Xu, DW; Peterson, C;
Indirizzi:
Linkoping Univ, Fac Hlth Sci, Dept Med & Care Clin Pharmacol, SE-58185 Linkoping, Sweden Linkoping Univ Linkoping Sweden SE-58185 col, SE-58185 Linkoping, Sweden Karolinska Hosp, Dept Pathol, Div Hematol, S-10401 Stockholm, Sweden Karolinska Hosp Stockholm Sweden S-10401 atol, S-10401 Stockholm, Sweden Karolinska Hosp, Dept Med, Div Hematol, S-10401 Stockholm, Sweden Karolinska Hosp Stockholm Sweden S-10401 atol, S-10401 Stockholm, Sweden
Titolo Testata:
HAEMATOLOGICA
fascicolo: 2, volume: 85, anno: 2000,
pagine: 124 - 132
SICI:
0390-6078(200002)85:2<124:HOIMCF>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
MULTIDRUG-RESISTANCE MDR1; MINIMAL RESIDUAL DISEASE; MAJOR VAULT PROTEIN; P-GLYCOPROTEIN; GENE-EXPRESSION; FLOW-CYTOMETRY; OVEREXPRESSION; PHENOTYPE; LRP;
Keywords:
acute myeloblastic leukemia; drug resistance multiple; flow cytometry; immunophenotyping; daunorubicin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Knaust, E Linkoping Univ, Fac Hlth Sci, Dept Med & Care Clin Pharmacol, SE-58185 Linkoping, Sweden Linkoping Univ Linkoping Sweden SE-58185 185 Linkoping, Sweden
Citazione:
E. Knaust et al., "Heterogeneity of isolated mononuclear cells from patients with acute myeloid leukemia affects cellular accumulation and efflux of daunorubicin", HAEMATOLOG, 85(2), 2000, pp. 124-132

Abstract

Background and Objectives. Pharmacologic studies on blasts from patients with leukemia are generally performed on density gradient isolated blood or bone marrow cells. Thereby, cellular drug accumulation and efflux are determined as mean values of the entire cell population. The objective of the present study was to characterize the heterogeneity in the accumulation and efflux of daunorubicin in various subpopulations of mononuclear cells isolated from patients with acute myeloid leukemia (AML). Design and Methods. Mononuclear cells from 33 patients with AML were Isolated from peripheral blood by density gradient centrifugation on Lymphoprep (1.077 g/mL). Cellular accumulation of fluorescent daunorubicin was determined by flow cytometry after incubation of the cells at +37 degrees C for 1 hour. Thereafter, the cells were washed and reincubated in drug-free medium. Kinetics of drug efflux were determined by frequent determination of cellular fluorescence during 30 min. Daunorubicin accumulation and efflux were compared in the total isolated mononuclear cell population and in the various blast cell populations gated on FSC/SSC according to the results of immunophenotyping. Results. In 8 of these 33 (24%) patient samples, two distinct blast cell populations could be identified. In 7 out of 8 these cases the more immatureblasts had a lower drug accumulation and in 6 out of the 8 cases also a higher efflux rate than the differentiating cell population. Cyclosporin A Increased daunorubicin accumulation and reduced efflux in the immature blast population. In the differentiating cell population cyclosporin A increased both the accumulation and the efflux. in patients with a single blast cell population, the gated blast cells had a significantly lower drug accumulation but also a lower drug efflux rate than the total cell population. Interpretation and Conclusions. The results imply that drug transport studies on cells isolated from patients with AML give somewhat different results depending on the cell population studied. Some, but not all, of these differences in daunorubicin accumulation and efflux as well as In the effect of cyclosporin A can be explained by a heterogenous expression of the mdr1-gene. The observed heterogeneity may be of special relevance with regard to drug resistance. The presence of even a small resistant cell clone may jeopardize the effect of the chemotherapy due to expansion resulting in relapseof disease. (C) 2000, Ferrata Storti Foundation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 07:42:09