Dasatinib for the treatment of chronic phase chronic myeloid leukemia

Victoria Campbell, Mhairi Copland

 Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder
driven by the oncogenic tyrosine kinase BCR-ABL. The discovery of the tyrosine kinase
inhibitor imatinib revolutionized the management of patients with CML. However, imatinib
can have significant side effects, and is not effective in all patients. The development of
second-generation (dasatinib and nilotinib) and third-generation (ponatinib) tyrosine kinase
inhibitors sought to address the issue of imatinib-resistance and -intolerance and furthermore,
to determine if these agents are superior to imatinib. Dasatinib, a multitargeted inhibitor, is
effective against most BCR-ABL kinase domain mutations resistant to imatinib and capable of
inducing faster and deeper molecular responses. This article describes the development of
dasatinib and documents its current clinical use in chronic phase CML.