Preclinical and clinical experience with dasatinib in philadelphia chromosome-negative leukemias and myeloid disorders

Recent advances in the molecular characterization of Philadelphia chromosome-negative (Ph−) leukemias and related myeloid disorders have provided a clear rationale for investigating novel targeted therapies. Dasatinib is a tyrosine kinase inhibitor with activity against BCR-ABL, platelet-derived growth factor receptors (PDGFRs), c- KIT, fibroblast growth factor receptors (FGFRs), SRC family kinases (SFKs), and EPHA receptors, all of which have been implicated in the pathogenesis of Ph− leukemias and myeloid disorders. This review presents emerging data on the preclinical and clinical activity of dasatinib in these diseases, which suggest that larger clinical studies are warranted.