A functional procedure using fresh samples to select patients with acute myeloid leukemia prior to treatment with the novel targeted cytotoxic agent F14512
2016
11087 Background: The Polyamine Transport System (PTS) is an energy-dependent machinery generally hyper-active in cancer cells with a high demand for polyamines. This system can be viewed as a suitable molecular gate to deliver selectively polyamine-based molecules into cancer cells. We exploited this strategy to target to PTS-positive cancer cells, F14512, a novel polyamine-epipodophyllotoxin conjugate, that exhibits significant anti-tumor activity and has been selected for further clinical development. This study was undertaken to investigate the potential of N-methyl-spermine-NBD, a proprietary fluorescent polyamine conjugate, designed to select patients with PTS-positive leukemic cells. Methods: The uptake of this probe was first measured by flow cytometry in a panel of human leukemia cell lines. The procedure was then adapted and optimized to measure N-methyl-spermine-NBD fluorescence in blood samples from healthy donors. After the selection of the optimal CD gating, median value of fluorescence of o...
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