Department of Hematology and Oncology, Charité-University Medicine, Berlin, Germany
Department of Hematology and Oncology, Charité-University Medicine, Berlin, Germany.
Anticancer Res. 2014 Sep;34(9):4899-907.
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.
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.
背景/目的：本研究旨在评估多靶点酪氨酸激酶抑制剂（TKI）TKI258 对婴幼儿急性淋巴细胞白血病（ALL），特别是携带混合谱系白血病（MLL）基因的 ALL 是否具有治疗价值。
采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法检测细胞增殖；流式细胞术检测细胞凋亡和细胞周期分布；Western blot 法检测蛋白水平的基因表达。
这些 ALL 细胞对 TKI258 治疗极为敏感，体外半数抑制细胞增殖浓度（IC50）值在纳摩尔范围内。与 mTOR 抑制剂 RAD001 联合应用，可观察到细胞死亡和增殖的协同作用。
TKI258 可能成为一种有效的治疗药物，无论是单独使用还是与 RAD001 联合使用，均可用于治疗 ALL，特别是具有 MLL 基因的实体。
