关键词: C-KIT基因突变, 核心结合因子相关性急性髓系白血病, 造血祖细胞, 免疫表型, 增殖

Abstract: Objective To investigate the molecular mechanism through which different C-KIT mutations influence the development of CBF-AML. Methods Assessment of exogenous KIT receptor and differentiation antigens on the surface of stably transfected EML cells was performed with flow cytometry; Cell proliferation in the presence or absence of IL-3 or Epo was analyzed using WST-1 cell proliferation assay; EpoR expression in different cell lines was identified with Western Blot assay. Results Human KIT receptor was expressed on the surface of transfected EML cells, Del417-419insY and D816V mutations led to a decrease in percentage of B220+ cells and an increase in Sca-1+ cells, albeit to a more extent for D816V mutation. Neither of them influenced positive percentage of CD34, Gr-1, Mac-1 and Ter119 in different cells. Del417-419insY mutant can cooperate with IL-3 or Epo to promote cell proliferation, while only IL-3 had a synergic effect with D816V mutant. Western Blot result confirmed the absence of EpoR expression in EML-D816V cells. Conclusion Distinct C-KIT mutations may differentially alter immunophenotype of hematopoietic progenitors and enhance cell proliferation, suggesting their relationship with development and prognosis of CBF-AML.

Key words: C-KIT mutations, CBF-AML, hematopoietic progenitors, immunophenotye, proliferation