SPOTLIGHT REVIEW Class effects of tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia

Tyrosine kinase inhibitors have revolutionized the treatment ofchronic myeloid leukemia (CML), offering patients severaltargeted therapeutic options that provide the possibility ofsustained remissions and prolonged survival. With the avail-ability of imatinib, nilotinib and dasatinib, physicians mustweigh the efficacy and safety profile of each agent whenchoosing the best therapeutic option for individual patients.Each agent targets tyrosine kinases within the cell uniquely tocause the desired antiproliferative effect. In addition to inhibit-ing the BCR-ABL kinase, imatinib and nilotinib target the samearray of other tyrosine kinases, including c-KIT and platelet-derived growth factor receptor (PDGFR), albeit with differingpotencies. While targeting BCR-ABL with the highest potencyamong approved agents in CML, dasatinib also targets a broadarray of off-target kinases, including SRC family members,PDGFR and EPHB4. The differences in kinase inhibition profilesamong these agents in vitro probably account for the differingclinical safety profiles of these agents. This paper reviews thevarious kinases inhibited by imatinib, nilotinib and dasatinib,and describes the potential impact of kinase inhibition on theefficacy and safety of each agent.Leukemia (2009) 23, 1698–1707; doi:10.1038/leu.2009.111;published online 28 May 2009Keywords: CML; imatinib; nilotinib; dasatinib; TKI; BCR-ABL