Integration of Next-Generation Sequencing to Treat Acute Lymphoblastic Leukemia with Targetable Lesions: The St. Jude Children's Research Hospital Approach
Integration of Next-Generation Sequencing to Treat Acute Lymphoblastic Leukemia with Targetable Lesions: The St. Jude Children's Research Hospital Approach
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DOI：
10.3389/fped.2017.00258
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发表时间：
2017-12-04
影响因子：
2.6
通讯作者：
Mullighan, Charles G.
中科院分区：
文献类型：
--
作者：
Inaba, Hiroto;Azzato, Elizabeth M.;Mullighan, Charles G.
急性淋巴细胞白血病(ALL)是儿童最常见的癌症类型。在圣犹大儿童研究医院最近进行的全面治疗研究中，ALL儿童的5年总存活率约为94%。这是基于白血病细胞生物学特征的风险分层和对治疗的反应(通过检测最小残留疾病来评估)、基于药效学和药物基因组数据的治疗修改以及改进的支持性护理相结合的结果。然而，需要创新的方法来进一步提高存活率，尽可能地接近100%，并减少治疗的不良影响。对白血病细胞DNA和RNA以及生殖系DNA的下一代测序可以识别促成白血病发生的亚微观遗传结构变化和序列变化。下一代测序数据可用于定义新的ALL亚型，帮助改善治疗反应和减少不良反应，并确定新的预后标志物和治疗靶点，以促进个性化精确医学。在这篇文章中，我们描述了我们通过下一代测序检测ALL患者靶向病变的方法，并解释了我们如何将测序数据整合到这些患者的治疗中。
Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children. In recent Total Therapy studies conducted at St. Jude Children's Research Hospital, children with ALL had a 5-year overall survival of around 94%. This is the result of a combination of risk stratification based on the biological features of the leukemic cells and the response to treatment (as assessed by the detection of minimal residual disease), treatment modification based on pharmacodynamic and pharmacogenomic data, and improved supportive care. However, innovative approaches are required to further improve survival to as close to 100% as possible and to reduce the adverse effects of treatment. Next-generation sequencing of leukemic cell DNA and RNA, as well as of germline DNA, can identify submicroscopic genetic structural changes and sequence alterations that contribute to leukemogenesis. Next-generation sequencing data can be used to define new ALL subtypes, to help improve treatment response and reduce adverse effects, and to identify novel prognostic markers and therapeutic targets to facilitate personalized precision medicine. In this article, we describe our approach to detecting targetable lesions in patients with ALL by next-generation sequencing and explain how we integrate the sequencing data into the treatment of these patients.