JC-1: a very sensitive fluorescent probe to test Pgp activity in adult acute myeloid leukemia.
One of the best-characterized resistance mechanisms in acute myeloid leukemia (AML) is the drug extrusion mediated by P-glycoprotein (Pgp). Recently the results of workshops organized by several groups concluded that accurate measurement of low activity of Pgp is a difficult goal in clinical samples. Therefore, highly sensitive and specific assays were developed to assess the functionality of Pgp using JC-1, a fluorescent molecule with the different emission wavelength (green and red fluorescence) according to its concentration in 129 AML samples. It was shown that JC-1 (green and red bands) may define 3 groups of patients: resistant (R) (29% of patients), intermediate (I) (36%), and sensitive (S) (35%). In contrast, rhodamine 123 assay detected only the R group defined by JC-1. Nevertheless, the I group has an intermediate expression of Pgp (0.39, 0.29, and 0.19 for the R, I, and S groups, respectively, P =.002), an intermediate biologic profile (percentage of CD34, 95%, 67%, and 44%, respectively, P <.0001; in vitro resistance to daunorubicin, 94 microM, 20 microM, and 12 microM, respectively, P =. 02), and an intermediate prognosis (achievement of complete remission, 55%, 65%, and 87%, P =.006; 3-year disease-free survival, 11%, 16%, and 36%, respectively, P =.005; and 3-year overall survival, 0%, 20%, and 51%, respectively, P <.0001). Therefore, JC-1 appeared to be a more convenient and simple way to detect a functional Pgp in clinical AML samples than rhodamine 123. (Blood. 2001;97:502-508)
Legrand
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Formation de Recherche Claude Bernard, Institut National de la Santé et de la Recherche Médicale (INSERM, E9912), Université Paris 6 (EA1529), France. legrand@htd.ap-hop-paris.fr
Perrot
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Simonin
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Baudard
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Marie
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D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000276:immunology / Q000378:metabolism*; D000208:Acute Disease; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001562:Benzimidazoles; D002232:Carbocyanines; D015331:Cohort Studies; D018572:Disease-Free Survival; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D007118:Immunoassay / Q000379:methods / Q000592:standards; D016130:Immunophenotyping; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism; D011379:Prognosis; D012235:Rhodamines; D012680:Sensitivity and Specificity; D013234:Stem Cells / Q000737:chemistry / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D001562:Benzimidazoles; D002232:Carbocyanines; D005456:Fluorescent Dyes; D009363:Neoplasm Proteins; D012235:Rhodamines; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine