JC-1: a very sensitive fluorescent probe to test Pgp activity in adult acute myeloid leukemia

Abstract

AbstractOne 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 μM, 20 μM, and 12 μM, 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.