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

Abstract

Background/aim: 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.

Materials and methods: 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.

Results: 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.

Conclusion: TKI258 may become a potent therapeutic agent, either alone or in combination with RAD001, for treatment of ALL, especially the entity with MLL genes.

Keywords: IC50 (concentration for 50% inhibition of cell proliferation); Infant and childhood ALL; cell apoptosis; cell proliferation; mTOR inhibitor RAD001; multi-tyrosine kinase inhibitor TKI258.