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Blood, 15 January 2001, Vol. 97, No. 2, pp. 502-508
NEOPLASIA
JC-1: a very sensitive fluorescent probe to test Pgp activity
in adult acute myeloid leukemia
Ollivier Legrand,
Jean-Yves Perrot,
Ghislaine Simonin,
Marion Baudard, and
Jean-Pierre Marie
From the formation de Recherche Claude Bernard,
Institut National de la Santé et de la Recherche Médicale
(INSERM, E9912), Université Paris 6 (EA1529), and the Services
d'Hématologic Biologique et clinique, Hôpital
Hôtel-Dieu, Paris, France.
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 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.
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