Growth inhibition of Ph+ progenitor cells from CML patients using the tyrosine kinase inhibitor CGP57148B

Background: Different methods have been investigated for their purging capa city of contaminating CML cells in autologous stem cell products. CGP57148B , a tyrphostin, has been shown to be efficient in the reduction of cell pro liferation of CML cell lines and primary CML cells, as well as in the inhib ition of bcr/abl-related tumor formation in animal models. Materials and me thods: The effect of CGP57148B on purified CD34(+) progenitor cells from BM , PB, or leukapheresis products of 8 CML patients was studied under serum-f ree cytokine-supplemented ex vivo culture conditions. Results: FISH as well as RT-PCR analysis showed a significant reduction of Ph+ cells after 7 day s ex vivo-culture in the presence of the tyrphostin. Growth of Ph- cells wa s almost unaffected by treatment with CGP57148B. Conclusion: Our results su pport the observation that CGP57148B can selectively inhibit proliferation of Ph+ / bcr/abl(+) primary CML cells under serum-free cytokine-supplemente d culture conditions.