De Keersmaecker Kim, Marynen Peter, Cools Jan
Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Leuven, Leuven, Belgium.
Haematologica. 2005 Aug;90(8):1116-27.
Over the past 20 years, a large number of genes involved in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) has been identified by molecular characterization of recurrent chromosomal aberrations and more subtle genetic defects. When reviewing the current list of oncogenes and tumor suppressor genes, it becomes clear that these can be grouped into four classes of mutations, which are involved in: (i) cell cycle deregulation; (ii) impaired differentiation; (iii) proliferation and survival advantage and (iv) unlimited self-renewal capacity. Based on recent studies of T-ALL, we can speculate that at least these four different mutations are required for the development of T-ALL. In this review we summarize our current insights into the molecular pathogenesis of T-ALL, and we discuss how these molecular findings provide new directions for future research and novel therapeutic strategies in T-ALL.
在过去20年中，通过对复发性染色体畸变和更细微的基因缺陷进行分子特征分析，已鉴定出大量参与T细胞急性淋巴细胞白血病（T-ALL）发病机制的基因。在审视当前的癌基因和肿瘤抑制基因列表时，很明显这些基因可分为四类突变，它们分别参与：（i）细胞周期失调；（ii）分化受损；（iii）增殖和生存优势；以及（iv）无限自我更新能力。基于最近对T-ALL的研究，我们可以推测T-ALL的发生至少需要这四种不同的突变。在本综述中，我们总结了目前对T-ALL分子发病机制的认识，并讨论了这些分子研究结果如何为T-ALL未来的研究和新的治疗策略提供新方向。
