Does initial responsiveness to imatinib have prognostic significance?

We have been examining intrinsic differences in the response of leukaemic cells to the drug at presentation, using Western Blotting to examine the inhibition of the tyrosine kinase activity of Bcr-ABL, which is its key leukaemogenic property. Surprisingly, we see a relatively wide variation in the IC50 (the drug concentration required to halve the enzymic activity of Bcr-Abl) of the drug for individual cases of CML. Our preliminary studies suggest that the IC50 is predictive of the rate of the response of patients to imatinib.

We are currently gathering data to determine if this has long term prognostic value, which may provide a means for identifying patients requiring more intensive therapy. 4. Imatinib (Glivec) inhibits the growth and differentiation of normal human monocytes.

Even though imatinib has specificity for the causative tyrosine kinase of chronic myeloid leukaemia, there is potential for this agent to affect normal cells by inhibiting other kinases. Our recent studies ... more.

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