Mastocytosis cells bearing a c-kit activating point mutation are characterized by hypersensitivity to stem cell factor and increased apoptosis

被引:13
作者
Dror, Y
Leaker, M
Caruana, G
Bernstein, A
Freedman, MH
机构
[1] Hosp Sick Children, Res Inst, Dept Pediat, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada
[2] Univ Toronto, Toronto, ON, Canada
[3] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Mol Biol & Canc, Toronto, ON M5G 1X5, Canada
关键词
mastocytosis; stem cell factor; c-kit; myelodys-plastic syndrome; apoptosis;
D O I
10.1046/j.1365-2141.2000.01935.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Mastocytosis is characterized by abnormal infiltration of mast cells into various organs. An activating mutation in c-kit, involving an A-->T substitution at nucleotide 2648 has recently been described in some patients with mastocytosis. We describe a 12-year-old girl with this mutation in her bone marrow cells at diagnosis with a myelodysplastic syndrome (MDS) without evidence of mastocytosis, and then in peripheral blood mononuclear cells 1 year later after the emergence of mastocytosis. The role of the c-Kit receptor and its ligand stem cell factor (SCF) in the pathogenesis of the disease was analysed in marrow clonogenic assays. We show that the genetic abnormalities in the patient resulted in factor-independent growth and hypersensitivity of primitive progenitors to SCE with increased production of mast cells. Increased apoptosis and cluster formation, consistent with the myelodysplastic nature of the disorder, accompanied accumulation of abnormal cells with increasing concentrations of SCF.
引用
收藏
页码:729 / 736
页数:8
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