Chromosomal translocation master genes, mouse models and experimental therapeutics
Chromosomal translocation master genes, mouse models and experimental therapeutics
复制标题
DOI：
10.1038/sj.onc.1204597
复制
发表时间：
2001-09-10
期刊：
影响因子：
8
通讯作者：
Rabbitts, TH
中科院分区：
文献类型：
--
作者：
Rabbitts, TH
分子生物学家通过在染色体易位连接处克隆癌基因或融合基因，阐明了染色体易位的一般原理。这些基因总是编码细胞内蛋白质，并且在急性癌症中，通常涉及转录和发育调节因子，其是细胞命运的主要调节因子（例如，涉及急性白血病的LMO2）。染色体易位通常与特定的细胞类型有关。这种密切联系的原因正在使用小鼠模型进行调查。我们正试图利用胚胎干细胞中的同源重组来模拟小鼠染色体易位的细胞特异性后果，以产生从头染色体易位或模拟这些易位的后果。此外，染色体易位基因及其产物是治疗的重要靶点。我们已经设计了新的治疗策略，其中包括内源性细胞通路的抗原特异性募集以影响细胞活力和一种新的反义结构形式以消除融合mRNA的功能。我们将在染色体易位的小鼠模型中评估这些程序，长期目标是完善用于表征患者特异性染色体易位的快速程序，以针对个体患者定制治疗。
Molecular biologists have elucidated general principles about chromosomal translocations by cloning oncogenes or fusion genes at chromosomal translocation junctions. These genes invariably encode intracellular proteins and in acute cancers, often involve transcription and developmental regulators, which are master regulators of cell fate (e.g. LMO2 which is involved in acute leukaemia). Chromosomal translocations are usually associated with specific cell types. The reason for this close association is under investigation using mouse models. We are trying to emulate the cell-specific consequences of chromosomal translocations in mice using homologous recombination in embryonic stem cells to generate de novo chromosomal translocations or to mimic the consequence of these translocations. In addition, chromosomal translocation genes and their products are important targets for therapy. We have designed new therapeutic strategies which include antigen-specific recruitment of endogenous cellular pathways to affect cellular viability and a novel structured form of antisense to ablate the function of fusion mRNAs. We will evaluate these procedures in the mouse models of chromosomal translocations and the long term aim is to perfect rapid procedures for characterizing patient-specific chromosomal translocations to tailor therapy to individual patients.