The in vitro activity of the tyrosine kinase inhibitor STI571 in BCR-ABL positive chronic myeloid leukaemia cells: synergistic interactions with anti-leukaemic agents.
Bottom Line: We have investigated whether the inhibition of this tyrosine kinase by the novel compound STI571 (formerly CGP57148B) would render K562, KU812 cell lines and chronic myeloid leukaemia-progenitor cells sensitive to induction of cell kill.Our data also showed synergy between STI571 and other anti-leukaemic agents; as an example, there were significant increases in per cent cell kill in cell lines cultured with both STI571 and etoposide compared to the two alone (per cent cell kill on day 3: 73.7+/-11.3 vs 44.5+/-8.7 and 17.8+/-7.0% in cultures with STI571 and etoposide alone respectively; P<0.001).This study confirms the central oncogenic role of BCR-ABL in the pathogenesis of chronic myeloid leukaemia, and highlights the role of targeting this tyrosine kinase as a useful tool in the clinical management of the disease.
Affiliation: Barry Reed Oncology Laboratory, 4th Floor, 38 Little Britain, St. Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK. email@example.comShow MeSH
Related in: MedlinePlus
Mentions: Flow cytometric analysis showed an increased number of cells undergoing apoptosis in cultures with STI571, with concomitant reductions in the other phases of the cell cycle. This was most clearly demonstrated in K562 cells treated with 5 μg ml−1 STI571 (Figure 2Figure 2
Affiliation: Barry Reed Oncology Laboratory, 4th Floor, 38 Little Britain, St. Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK. firstname.lastname@example.org