文章：

T细胞急性淋巴细胞白血病的遗传学和机制

The genetics and mechanisms of T cell acute lymphoblastic leukaemia

原文发布日期：2016-07-25

DOI: 10.1038/nrc.2016.63

类型: Review Article

开放获取: 否

要点：

1. T cell acute lymphoblastic leukaemia (T-ALL) is an aggressive haematological tumour resulting from the malignant transformation of T cell progenitors.
2. T-ALL is biologically and genetically heterogeneous with gene expression signatures that identify different clinico-biological groups associated with T cell arrest at different stages of thymocyte development.
3. Oncogenic NOTCH signalling resulting from activating mutations in NOTCH1 is a major driver of T-ALL transformation.
4. Aberrant expression of transcription factor oncogenes as a result of chromosomal translocations and other chromosomal rearrangements is common in T-ALL.
5. Recurrent mutations and deletions in T-ALL frequently involve cell cycle regulators, but also transcription factors, tumour suppressors, epigenetic factors and negative regulators of NOTCH1, Janus kinase (JAK)–signal transducer and activator of transcription (STAT), PI3K and MAPK signalling.
6. Relapsed T-ALL is associated with a poor prognosis, and relapse-associated activating mutations in the cytosolic 5′-nucleotidase II gene, NT5C2, induce resistance to 6-mercaptopurine chemotherapy.

要点翻译：

1. T细胞急性淋巴细胞白血病（T-ALL）是一种侵袭性血液肿瘤，源于T细胞祖细胞的恶性转化。
2. 该疾病在生物学和遗传学上具有异质性，其基因表达特征可识别不同的临床生物学亚群，这些亚群与胸腺细胞发育不同阶段的T细胞阻滞相关。
3. 由NOTCH1基因激活突变致病的致癌性NOTCH信号通路是驱动T-ALL转化的主要因素。
4. 由于染色体易位和其他染色体重排导致的转录因子癌基因异常表达在T-ALL中较为常见。
5. T-ALL中频发的突变和缺失不仅涉及细胞周期调控因子，还包括转录因子、肿瘤抑制因子、表观遗传因子以及NOTCH1、Janus激酶（JAK）-信号转导与转录激活因子（STAT）、PI3K和MAPK信号通路的负调控因子。
6. 复发型T-ALL预后不良，其复发相关的胞质5′-核苷酸酶II基因（NT5C2）激活突变会诱导对6-巯基嘌呤化疗的耐药性。

英文摘要：

T cell acute lymphoblastic leukaemia (T-ALL) is an aggressive haematological malignancy derived from early T cell progenitors. In recent years genomic and transcriptomic studies have uncovered major oncogenic and tumour suppressor pathways involved in T-ALL transformation and identified distinct biological groups associated with prognosis. An increased understanding of T-ALL biology has already translated into new prognostic biomarkers and improved animal models of leukaemia and has opened opportunities for the development of targeted therapies for the treatment of this disease. In this Review we examine our current understanding of the molecular mechanisms of T-ALL and recent developments in the translation of these results to the clinic.

摘要翻译： 

T细胞急性淋巴细胞白血病（T-ALL）是一种源于早期T细胞前体的侵袭性血液系统恶性肿瘤。近年来，基因组学和转录组学研究揭示了参与T-ALL转化的主要致癌和抑癌通路，并鉴定出与预后相关的不同生物学亚群。对T-ALL生物学的深入理解已转化为新的预后生物标志物、更完善的白血病动物模型，并为开发该病的靶向治疗创造了机会。本综述探讨了我们对T-ALL分子机制的最新认识，以及这些研究成果向临床转化的最新进展。

原文链接：

The genetics and mechanisms of T cell acute lymphoblastic leukaemia