Department of Pathology, The University of Chicago, Chicago, IL 60637, USA.
Blood Cells Mol Dis. 2014 Jan;52(1):68-75. doi: 10.1016/j.bcmd.2013.07.003. Epub 2013 Jul 30.
The BCL6 gene, which is expressed in certain B- and T-cell human lymphomas, is involved with chromosomal rearrangements and mutations in a number of these neoplasms. Lymphomagenesis is believed to evolve through a multi-step accumulation of genetic alterations in these tumors. We used retroviral insertional mutagenesis in transgenic mice expressing the human BCL6 transgene in order to identify genes that cooperate with BCL6 during lymphomatous transformation. We previously reported PIM1 as the most frequently recurring cooperating gene in this model. We now report three newly identified cooperating genes-GFI1B, EVI5, and MYB-that we identified in the lymphomas of retroviral-injected BCL6 transgenic mice (but not in retroviral-injected non-transgenic controls); mRNA and protein expression of GFI1B and EVI5 were decreased in the murine tumors, whereas MYB mRNA and protein expression were increased or decreased. These findings correlated with protein expression in human lymphomas, both B- and T-cell. Improved therapy of lymphomas may necessitate the development of combinations of drugs that target the alterations specific to each neoplasm.
BCL6 基因在某些人类 B 细胞和 T 细胞淋巴瘤中表达，与这些肿瘤中的许多染色体重排和突变有关。淋巴瘤的发生被认为是通过这些肿瘤中遗传改变的多步积累而发展的。我们使用在表达人类 BCL6 转基因的转基因小鼠中使用逆转录病毒插入诱变，以鉴定在淋巴瘤转化过程中与 BCL6 合作的基因。我们之前报道 PIM1 是该模型中最常出现的合作基因。我们现在报告了三个新鉴定的合作基因-GFI1B、EVI5 和 MYB-在我们从逆转录病毒注射的 BCL6 转基因小鼠的淋巴瘤中鉴定到（而不是在逆转录病毒注射的非转基因对照中）；GFI1B 和 EVI5 的 mRNA 和蛋白表达在鼠肿瘤中降低，而 MYB mRNA 和蛋白表达增加或减少。这些发现与人类 B 细胞和 T 细胞淋巴瘤的蛋白表达相关。淋巴瘤的改良治疗可能需要开发针对每个肿瘤特有的改变的药物组合。
