John Libbey Eurotext

Bulletin du Cancer

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Leukemogenesis and new therapy development: the example of chronic myelogenous leukemia Volume 88, issue 7, Juillet 2001

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Authors
Laboratoire de greffe de moelle, Université Victor-Ségalen UMR CNRS 5540, 146, rue Léo-Saignat, 33076 Bordeaux.
  • Key words: chronic myeloid leukemia, Philadelphia chromosome, tyrosine kinase activity, STI571
  • Page(s) : 651-8
  • Published in: 2001

During the past ten years, the improvements of our understanding of cellular signal transduction pathways provide new targets for drug therapies. Chronic myeloid leukemia (CML), a malignant hematopoietic stem cell disorder, is characterised by an acquired genetic abnormality: the Philadelphia chromosome (Ph) and its molecular counterpart, the oncogene BCR-ABL. The latter, which is translated in an active BCR-ABL protein, exhibited a deregulated tyrosine kinase activity inducing malignant transformation. Produced from the 2-phenylaminopyrimidine class, a novel synthetic inhibitor, identified as CGP57148 (STI571), inhibits tyrosine kinase activity of c-ABL, BCR-ABL, PDGF-R and c-kit at micromolar concentrations. It suppresses the proliferation of the majority of BCR-ABL positive cell lines. The phases I-II clinical trials in CML have demonstrated promising results, especially in the chronic phase of the disease. STI571 is an original therapeutic approach which may be used as a model for the development of other drugs in cancer.