title: Systemic mastocytosis: current classification and novel therapeutic options.
abstract: Systemic mast cell disease is characterized by dysregulated mast cell growth and survival, with infiltration into multiple organs and release of systemic mediators. Much has been learned about mast cell biology over the past 20 years, and it has become apparent that activating mutations in the c-KIT receptor tyrosine kinase underlie the aberrant cell signaling and mast cell growth in a majority of patients. Despite this knowledge, targeted therapy with imatinib has been largely unsuccessful due to resistance of the common c-KIT D816V (Asp-->Val) mutation. Novel strategies designed to inhibit the growth of mast cells containing the c-KIT D816V mutations have shown success in vitro and may provide effective targeted therapy for this treatment-refractory disease.
authors.affiliation: Department of Medical Oncology/Hematologic Malignancies at Dana-Farber Cancer Institute and Massachusetts General Hospital, Boston, MA 02115, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Barbie
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Deangelo
mesh_terms: D001549:Benzamides; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D000068877:Imatinib Mesylate; D008407:Mast Cells / Q000201:enzymology / Q000473:pathology; D034721:Mastocytosis, Systemic / Q000145:classification* / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000266:history; D020125:Mutation, Missense; D010879:Piperazines / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit