Article
Resistance to multiple novel antifolates is mediated via defective drug transport resulting from clustered mutations in the reduced folate carrier gene in human leukaemia cell lines.
The Biochemical journal - 1 Nov 2002
Rothem Lilah, Ifergan Ilan, Kaufman Yotam, Priest David G, Jansen Gerrit, Assaraf Yehuda G
Abstract excerpt
We have studied the molecular basis of resistance of multiple human leukaemia CCRF-CEM sublines to the novel antifolates ZD9331, GW1843, AG2034, PT523 and edatrexate, which use the reduced folate carrier (RFC) as their main cellular uptake route and that target different folate-dependent enzymes. Antifolate-resistant sublines established by stepwise and single-step selections displayed up to 2135-fold resistance...
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