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一种表达p230 BCR/ABL融合蛋白的费城染色体新型白血病细胞系的建立及分子特征分析

Establishment and molecular characterization of a novel leukemic cell line with Philadelphia chromosome expressing p230 BCR/ABL fusion protein.

作者信息

Wada H, Mizutani S, Nishimura J, Usuki Y, Kohsaki M, Komai M, Kaneko H, Sakamoto S, Delia D, Kanamaru A

机构信息

Department of Virology, National Children's Medical Research Center, Tokyo, Japan.

出版信息

Cancer Res. 1995 Jul 15;55(14):3192-6.

PMID:7606740
Abstract

The cell line AR230 was established from the peripheral blood mononuclear cells of a patient with chronic myeloid leukemia and t(9;22) translocation bearing a variant type of BCR/ABL rearrangement. AR230 expresses a BCR/ABL fusion protein with a molecular mass of 230 kilodaltons (kDa) due to the insertion of 180 amino acids encoded by 3' exons of BCR (b4 to c3). An immune complex kinase assay showed that the 230-kDa BCR/ABL protein ahd autophosphorylation activity. Immunoprecipitation analysis revealed a stable complex of GRB2 and 230-kDa BCR/ABL proteins, indicating that the Ras activation pathway is involved in the process of transformation. AR230 expressed another short transcript consisting of a BCRc2/ABL junction, which is associated with a stop signal shortly after the junction. To our knowledge, this is the first cell line expressing a 230-kDa fusion product of BCR/ABL. AR230 will be useful for studying the biological function of divergent BCR/ABL proteins.

摘要

细胞系AR230是从一名患有慢性髓性白血病且发生t(9;22)易位并带有变异型BCR/ABL重排的患者外周血单个核细胞中建立的。由于BCR的3'外显子(b4至c3)编码的180个氨基酸的插入,AR230表达一种分子量为230千道尔顿(kDa)的BCR/ABL融合蛋白。免疫复合物激酶分析表明,230-kDa的BCR/ABL蛋白具有自磷酸化活性。免疫沉淀分析揭示了GRB2和230-kDa的BCR/ABL蛋白形成稳定复合物,表明Ras激活途径参与了转化过程。AR230表达另一种由BCRc2/ABL连接组成的短转录本,该连接在连接后不久与一个终止信号相关。据我们所知,这是第一个表达230-kDa BCR/ABL融合产物的细胞系。AR230将有助于研究不同BCR/ABL蛋白的生物学功能。

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