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Anticancer research

TKI258, a multi-tyrosine kinase inhibitor is efficacious against human infant/childhood lymphoblastic leukemia in vitro.


PMID 25202072

Abstract

The goal of the present study was to evaluate if the multiple tyrosine kinase inhibitor (TKI) TKI258 has any treatment value for infant/childhood acute lymphoblatic leukemia (ALL), especially those ALLs bearing the mixed lineage leukemia (MLL) genes. Cell proliferation was measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; cell apoptosis and cell-cycle distribution with flow cytometry. Gene expression at the protein level was determined by western blotting. These ALL cells were extremely sensitive to TKI258 treatment with a concentration for 50% inhibition of cell proliferation (IC50) values in the nanomolar range in vitro. By combination with mTOR inhibitor RAD001, a synergistic effect on cell death and cell proliferation was observed in these cells. TKI258 may become a potent therapeutic agent, either alone or in combination with RAD001, for treatment of ALL, especially the entity with MLL genes.