期刊
LEUKEMIA RESEARCH
卷 30, 期 11, 页码 1365-1370出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2006.04.005
关键词
c-kit kinase inhibitor; AMN107; imatinib; mastocytosis
Most adults with systemic mastocytosis (SM) carry an activating mutation in the codon 816 of c-kit. We investigated the activity of the new tyrosine kinase inhibitor AMN107 on c-kit mutated mast cell lines and bone marrow samples from patients with SM and compared it to that of imatinib mesylate, a tyrosine kinase inhibitor effective in some patients with SM. In HMC-1(560) mast cells carrying wild-type codon 816 c-kit, AMN107 was very effective and as potent as imatinib in inhibiting cellular proliferation and inducing apoptosis (P < 0.0823). By contrast, in HMC-1(560,816) cells bearing a c-kit mutation in codon 816, neither drug exerted a significant effect (P < 0.0015). AMN 107 was also as effective as imatimb in inhibiting phosphorylation of c-kit in HMC-1(560) cells. However, AMN107 had little effect on ex vivo survival of bone marrow mast cells with 816 c-kit mutation obtained from patients with SM. Based upon our results, AMN107 and imatinib are equipotent against mast cells with wild-type c-kit and those harboring the juxtamembrane D560G c-kit mutant but have no significant activity over the dose range tested against cells expressing the c-kit D816V mutant tyrosine kinase. (c) 2006 Elsevier Ltd. All rights reserved.
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