Acute myeloid leukemia cells with low P-glycoprotein expression and high Rhodamine 123 efflux capacity display high clonogenicity

Abstract

This study was designed to correlate the clonogenic capacity of acute myeloid leukemia (AML) cells with P-glycoprotein (Pgp) expression level and P-gp-mediated efflux capacity. Fifty AML cell samples were tested for P-gp expression using MRK16 monoclonal antibody and flow cytometry. Among them, 12 samples were selected for sorting experiments according to the following two criteria: their clonogenic capacity in methylcellulose in the presence of 5637 conditioned medium, and the heterogeneity of P-gp distribution in leukemic cells. For each of these 12 samples, leukemic cells which displayed the highest P-gp expression level (P-gp ؉؉ ) and P-gp ؊ leukemic cells were sorted after MRK16 staining and seeded into methylcellulose for primary clonogenic assay. In each case, the number of CFU-L in the P-gp − fraction was significantly higher than that of the P-gp dull and Rh 123 bright populations, respectively. Altogether this study suggests that, for an individual AML cell population, the clonogenic fraction is preferentially recruited in AML cells which display low P-gp expression and high P-gp-mediated efflux capacity.

Genetic Polymorphisms in ABCB1 Influence the Pharmacodynamics of Tacrolimus

“…5 Here we hypothesized that the 3435C.T SNP in the ABCB1 gene can modulate the immunosuppressive activity of tacrolimus by altering the activity of the pump. [18][19][20] The T cells with the highest ABCB1 efflux activity are memory CD4 + and CD8 + T cells, 9,21 a population with low susceptibility to tacrolimus 22 and important in the transplantation setting because they are pivotal for alloreactivity. 2).…”

Impact of Small Molecules Immunosuppressants on P-Glycoprotein Activity and T-cell Function

“…The specific role of Pgp modulators and their kinetic profile is thus essential to fully characterize and approach the broad properties of immunosuppressive drugs (31), Laurent G et al (32) and Gupta et al (33) clearly showed that the expression of Pgp was higher in CD4 + than in CD8 + T cells. Functionally, Pgp was more efficient in the CD8 + subpopulation.…”

Expression of β-catenin by acute myeloid leukemia cells predicts enhanced clonogenic capacities and poor prognosis

“…[22][23] Briefly, 3 Â 10 5 cells were resuspended in methyl-cellulose semi-solid medium with (PE1 þ , Plating Efficiency at 1 week) or without (PE1-) 10% human bladder carcinoma cell line 5637 conditioned medium (5637 CM). A total of 1 Â 10 5 cells was then plated in 35 mm Petri dishes in triplicate (1 ml mixture/dish), and incubated at 371C and 5% CO 2 humidified atmosphere.…”