A farnesyltransferase inhibitor increases survival of mice with very advanced stage acute lymphoblastic leukemia/lymphoma caused by P190 Bcr/Abl.

摘要: Treatment of chronic myelogenous leukemia with a specific inhibitor the Bcr/Abl tyrosine kinase, imatinib, has shown great promise. However, acute lymphoblastic leukemias that express only transiently respond to imatinib. Therefore, alternative treatments for this type are urgently needed. Here, we examined activity farnesyltransferase SCH66336 as single chemotherapeutic agent in nude mouse model representative very advanced stage P190-positive leukemia/lymphoma. Our results show oral administration was able significantly increase survival these mice compared controls treated vehicle (P<0.005), and caused marked regression tumor burden mice. Upon prolonged treatment, lymphomas re-emerged subset cells from two such tested survive presence increased concentrations SCH66336. The same cells, however, remained sensitive towards A combination drugs, preceded by therapy reduce initial burden, could be effective treatment Ph-positive ALL. We conclude SCH66336, on its own, is remarkably eradicating large numbers lymphoma causing visible reduction size, minimal toxicity.