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: Proliferation assays showed STI571 to be an effective cytotoxic agent in chronic myeloid leukaemia-derived cell lines (IC(50) on day 5 of 4.6 microg ml(-1) and 3.4 microg ml(-1) for K562 and KU812 respectively) and in leukaemic blast cells (per cent viability on day 3 at 4 microg ml(-1): 55.5+/-8.7 vs 96.4+/-3.7%).STI571 also appeared to specifically target bcr-abl expressing cells, as results from colony forming assays using the surviving cell fraction from STI571-treated peripheral CD34(+) chronic myeloid leukaemia blast cells, indicated a reduction in the expansion of colonies of myeloid lineage, but no effect on normal colony formation.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).
Affiliation: Barry Reed Oncology Laboratory, 4th Floor, 38 Little Britain, St. Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK. firstname.lastname@example.orgShow MeSH
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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. email@example.com