Beyond Chronic Myelogenous Leukemia: Potential Role for Imatinib in Philadelphia-Negative Myeloproliferative Disorders

摘要: The myeloproliferative disorders (MPDs) are chronic malignant conditions originating from the clonal expansion of a multipotential hematopoietic stem cell. These diseases include polycythemia vera (PV), essential thrombocythenia, atypical myeloid leukemia, idiopathic hypereosinophilic syndrome (HES), agnogenic metaplasia with myelofibrosis, and others. Receptor tyrosine kinases—the platelet-derived growth factor receptors (PDGFRs) c-Kit—and their respective ligands have been implicated in pathogenesis MPDs. For example, constitutively activated PDGFR fusion kinase (FIP1L1-PDGFRA) was identified some patients HES, disease characterized by sustained overproduction eosinophils that has classified World Health Organization as subtype Imatinib is selective inhibitor PDGFRs, c-Kit, Abl Arg protein-tyrosine kinases, well Bcr-Abl, oncogenic causes leukemia. efficacy imatinib treating systemic mast cell disease, myelomonocytic leukemia associated PDGFRβ genes, (to lesser extent) PV myelofibrosis reviewed institutional experience review literature. In 3 studies involved 11 PV, 10 had reductions phlebotomy imatinib. Eight 42 HES indicated 70% achieved complete hematologic remissions Four 6 MPD responses 5 patients. Insight into molecular MPDs will improve definitions different categories suggests signal transduction inhibition likely to be an increasingly important treatment option future. Cancer 2004. © 2004 American Society.