The potential for dasatinib in treating chronic lymphocytic leukemia, acute myeloid leukemia, and myeloproliferative neoplasms

Dasatinib is a kinase inhibitor that inhibits BCR--ABL, Src family kinases, c-Kit, and platelet-derived growth factor receptor kinase. It is licensed for the first- and second-line treatment of chronic myeloid leukemia and second-line treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia on the basis of BCR--ABL inhibition, but the activity of dasatinib against additional molecular targets may enable treatment of other hematologic disorders. Potential targets for dasatinib in chronic lymphocytic leukemia (CLL) include Lyn (a Src family kinase), ABL, and the associated CD40 pathway. Although dasatinib monotherapy has modest clinical activity in CLL, ongoing studies are evaluating combination treatment. In acute myeloid leukemia (AML), FLT3, Lyn, c-Kit, and BCR--ABL are expressed in a subpopulation of patients. To date, clinical responses to dasatinib in patients with unselected AML have been mixed and larger studies are needed, particularly correlating clinical response to molecular markers. Imatinib has been used successfully to treat patients with chronic eosinophilic disorders with the FIP1L1--PDGFRA fusion kinase; limited clinical data indicate that dasatinib could be active in imatinib-resistant disease. Ongoing clinical studies should further define the value of dasatinib in these disorders.</.