文章：

FHL2与CALM相互作用，在急性红系白血病中高表达

FHL2 interacts with CALM and is highly expressed in acute erythroid leukemia

原文发布日期：2011-11-11

DOI: 10.1038/bcj.2011.40

类型: Original Article

开放获取: 是

英文摘要：

The t(10;11)(p13;q14) translocation results in the fusion of the CALM (clathrin assembly lymphoid myeloid leukemia protein) and AF10 genes. This translocation is observed in acute myeloblastic leukemia (AML M6), acute lymphoblastic leukemia (ALL) and malignant lymphoma. Using a yeast two-hybrid screen, the four and a half LIM domain protein 2 (FHL2) was identified as a CALM interacting protein. Recently, high expression of FHL2 in breast, gastric, colon, lung as well as in prostate cancer was shown to be associated with an adverse prognosis. The interaction between CALM and FHL2 was confirmed by glutathione S-transferase-pulldown assay and co-immunoprecipitation experiments. The FHL2 interaction domain of CALM was mapped to amino acids 294–335 of CALM. The transcriptional activation capacity of FHL2 was reduced by CALM, but not by CALM/AF10, which suggests that regulation of FHL2 by CALM might be disturbed in CALM/AF10-positive leukemia. Extremely high expression of FHL2 was seen in acute erythroid leukemia (AML M6). FHL2 was also highly expressed in chronic myeloid leukemia and in AML with complex aberrant karyotype. These results suggest that FHL2 may play an important role in leukemogenesis, especially in the case of AML M6.

摘要翻译： 

t(10;11)(p13;q14)易位导致CALM（网格蛋白组装淋巴髓系白血病蛋白）与AF10基因融合。该易位现象可见于急性髓母细胞白血病（AML M6）、急性淋巴细胞白血病（ALL）及恶性淋巴瘤。通过酵母双杂交筛选，鉴定出四个半LIM结构域蛋白2（FHL2）是CALM的相互作用蛋白。近期研究表明，FHL2在乳腺癌、胃癌、结肠癌、肺癌及前列腺癌中的高表达与不良预后相关。谷胱甘肽S-转移酶下拉实验和免疫共沉淀实验证实了CALM与FHL2的相互作用。CALM的FHL2相互作用结构域定位于其第294-335位氨基酸。CALM能降低FHL2的转录激活能力，而CALM/AF10融合蛋白无此功能，提示在CALM/AF10阳性白血病中CALM对FHL2的调控可能被破坏。急性红系白血病（AML M6）中可见FHL2的极高表达。FHL2在慢性髓系白血病和伴有复杂异常核型的急性髓系白血病中同样高表达。这些结果表明FHL2可能在白血病发生中起重要作用，尤其在AML M6病例中。

原文链接：

FHL2 interacts with CALM and is highly expressed in acute erythroid leukemia