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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Antineoplastic Agents, Apoptosis, Benzimidazoles, Cell Line, Tumor, Cell Proliferation, Drug Synergism, Everolimus, Fusion Proteins, bcr-abl, Humans, Leukemia, Protein Kinase Inhibitors, Quinolones, Sirolimus, TOR Serine-Threonine Kinases.
user
Is the multi-tyrosine kinase inhibitor TKI258 , alone or in combination with RAD001 , effective for treatment of human leukemia with BCR-ABL translocation in vitro? Context: BCR-ABL-positive (BCR-ABL(+)) leukemia is very difficult to treat although much improvement has been achieved due to the clinical application of imatinib and the second-generation tyrosine kinase inhibitors (TKIs). This study aimed to evaluate for the first time the treatment value of the multiple tyrosine kinase inhibitor TKI258 in BCR-ABL(+) leukemia. Proliferation of different BCR-ABL(+) leukemic cells was measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; cell apoptosis with Annexin V/propidium iodide (PI) and flow cytometry. Gene expression at the protein level was determined by western blotting. This drug showed treatment efficacy in naïve and imatinib-resistant BCR-ABL(+) leukemia cells, particularly in cells harboring T315I-mutated BCR-ABL, for which no effective inhibitor is available to date. By combination with the mTOR inhibitor RAD001, a synergistic effect on cell proliferation was observed in these cell lines.
assistant
TKI258 may become a potent therapeutic agent, either alone or in combination with RAD001, for treatment of BCR-ABL(+) leukemia. Final Decision: yes