Genomic characterization of childhood acute lymphoblastic leukemia.
Genomic characterization of childhood acute lymphoblastic leukemia.
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DOI：
10.1053/j.seminhematol.2013.10.001
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发表时间：
2013-10
影响因子：
3.6
通讯作者：
Mullighan CG
中科院分区：
文献类型：
--
作者：
Mullighan CG
急性淋巴细胞白血病（ALL）是最常见的儿童恶性肿瘤，也是儿童癌症死亡的主要病例。在过去的十年里，我们对ALL遗传基础的理解发生了转变，这是由于对大量儿童ALL进行了详细的综合基因组分析。最初使用基于微阵列的方法，以及最近使用下一代测序，这些研究使得能够对ALL进行更精确的子分类，并且已经表明每个ALL实体的特征在于通常扰乱关键细胞途径的结构和序列突变的星座，包括淋巴发育、细胞周期调节、肿瘤抑制、Ras和酪氨酸激酶驱动的信号传导和表观遗传调节。重要的是，一些新发现的遗传改变已经进入临床，以改善诊断和风险分层，并正在寻求作为治疗干预的新靶点。ALL的研究也引领了对癌症亚克隆异质性的剖析，并表明个体患者通常具有多个相关但遗传上不同的亚克隆，这种遗传决定的克隆异质性是复发的重要决定因素。此外，全基因组分析已经确定了影响ALL风险的遗传性遗传变异。正在进行的研究正在部署详细的整合遗传转录组学和表观遗传测序，以全面定义ALL的基因组景观。本文综述了我们对ALL遗传学的理解的最新进展，重点是那些具有重要致病或治疗意义的改变。
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and a leading case of childhood cancer death. The last decade has witnessed a transformation in our understanding of the genetic basis of ALL due to detailed integrative genomic profiling of large cohorts of childhood ALL. Initially using microarray based approaches, and more recently with next-generation sequencing, these studies have enabled more precise sub-classification of ALL, and have shown that each ALL entity is characterized by constellations of structural and sequence mutations that typically perturb key cellular pathways including lymphoid development, cell cycle regulation, tumor suppression, Ras- and tyrosine kinase driven signaling, and epigenetic regulation. Importantly, several of the newly identified genetic alterations have entered the clinic to improve diagnosis and risk stratification, and are being pursued as new targets for therapeutic intervention. Studies of ALL have also led the way in dissecting the subclonal heterogeneity of cancer, and have shown that individual patients commonly harbor multiple related but genetically distinct subclones, and that this genetically determined clonal heterogeneity is an important determinant of relapse. In addition, genome-wide profiling has identified inherited genetic variants that influence ALL risk. Ongoing studies are deploying detailed integrative genetic transcriptomic and epigenetic sequencing to comprehensively define the genomic landscape of ALL. This review describes the recent advances in our understanding of the genetics of ALL, with an emphasis on those alterations of key pathogenic or therapeutic importance.
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影响因子：
51.1
作者：
Den Boer, Monique L.;van Slegtenhorst, Marjon;De Menezes, Renee X.;Cheok, Meyling H.;Buijs-Gladdines, Jessica G. C. A. M.;Peters, Susan T. C. J. M.;Van Zutven, Laura C. M.;Beverloo, H. Berna;Van der Spek, Peter J.;Escherich, Gaby;Horstmann, Martin A.;Janka-Schoub, Gritta E.;Kamps, Willem A.;Evans, William E.;Pieters, Rob
通讯作者：
Pieters, Rob
影响因子：
11.4
作者：
通讯作者：
--
影响因子：
20.3
作者：
Harvey, Richard C.;Mullighan, Charles G.;Willman, Cheryl L.
通讯作者：
Willman, Cheryl L.
影响因子：
168.9
作者：
Bercovich, Dani;Ganmore, Ithamar;Izraeli, Shai
通讯作者：
Izraeli, Shai
影响因子：
6.5
作者：
Harrison, CJ;Moorman, AV;Martineau, M
通讯作者：
Martineau, M