The genetics and molecular biology of T-ALL.
The genetics and molecular biology of T-ALL.
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DOI：
10.1182/blood-2016-10-706465
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发表时间：
2017-03-02
期刊：
影响因子：
20.3
通讯作者：
De Keersmaecker K
中科院分区：
文献类型：
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作者：
Girardi T;Vicente C;Cools J;De Keersmaecker K
T 细胞急性淋巴细胞白血病 (T-ALL) 是一种侵袭性恶性肿瘤，由影响 T 细胞发育的基因组病变累积引起。多年来，人们已经确定转录因子表达失调、CDKN2A/2B 细胞周期调节因子受损以及 NOTCH1 信号传导过度活跃在这种白血病的发病机制中发挥着重要作用。在过去的十年中，通过高分辨率拷贝数阵列和下一代测序技术对 T-ALL 基因组进行系统筛查表明，T 细胞祖细胞积累了影响 JAK/STAT 信号传导、蛋白质翻译和表观遗传控制的额外突变，为治疗提供了新的有吸引力的靶点。在这篇综述中，我们提供了有关 T-ALL 发病机制、引入靶向治疗的机会以及仍然面临的挑战的最新知识。
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy caused by the accumulation of genomic lesions that affect the development of T-cells. Since many years, it has been established that deregulated expression of transcription factors, impairment of the CDKN2A/2B cell cycle regulators and hyperactive NOTCH1 signaling play prominent roles in the pathogenesis of this leukemia. In the past decade, systematic screening of T-ALL genomes by high resolution copy number arrays and next- generation sequencing technologies has revealed that T-cell progenitors accumulate additional mutations affecting JAK/STAT signaling, protein translation and epigenetic control, providing novel attractive targets for therapy. In this review, we provide an update on our knowledge on T-ALL pathogenesis, on the opportunities for the introduction of targeted therapy and on the challenges that are still ahead.