The in vitro activity of the tyrosine kinase inhibitor STI571 in BCR-ABL positive chronic myeloid leukaemia cells: synergistic interactions with anti-leukaemic agents.

摘要: Chronic myeloid leukaemia is typically characterised by the presence of dysregulated BCR–ABL tyrosine kinase activity, which central to oncogenic feature being resistant a wide range cytotoxic agents. We have investigated whether inhibition this novel compound STI571 (formerly CGP57148B) would render K562, KU812 cell lines and chronic leukaemia-progenitor cells sensitive induction kill. Proliferation assays showed be an effective agent in leukaemia-derived (IC50 on day 5 4.6 μg ml−1 3.4 μg ml−1 for K562 respectively) leukaemic blast (per cent viability 3 at 4 μg ml−1: 55.5±8.7 vs 96.4±3.7%). also appeared specifically target bcr–abl expressing cells, as results from colony forming using surviving fraction STI571-treated peripheral CD34+ indicated reduction expansion colonies lineage, but no effect normal formation. Our data synergy between other anti-leukaemic agents; example, there were significant increases per kill cultured with both etoposide compared two alone 3: 73.7±11.3 44.5±8.7 17.8±7.0% cultures respectively; P<0.001). This study confirms role pathogenesis leukaemia, highlights targeting useful tool clinical management disease.