Genetic Landscape of Acute Myeloid Leukemia (AML) in Older Patients

老年患者急性髓系白血病 (AML) 的遗传概况

• 批准号: 387876113
• 负责人: Professor Dr. Lars Bullinger
• 金额: --
• 依托单位: Klinik für Innere Medizin III
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/387876113?language=en
• 关键词: Genetic; Landscape; Acute; Myeloid; Leukemia

In recent years, the development of next-generation sequencing (NGS) techniques have greatly advanced our understanding of the molecular pathogenesis of AML. However, most studies on the genomic profiling of AML stem from younger adult patients. From smaller studies in older patients there is increasing evidence that the (epi)genetic profile in older patients greatly differs from that of younger patients. The specific aims of the proposed project are: Evaluation of the mutational spectrum, identification of patterns of co-mutations and mutual exclusivities in a cohort of at least 1,000 older AML patients using targeted DNA sequencing, and refinement of the genomic classification of older AML; identification of prognostic and predictive factors to treatment with hypomethylating agents, and establishment of a new genetic risk classification applicable for older patients; generation of epigenetic signatures; transcriptional profiling (RNA-seq) using the novel Oxford Nanopore technology for detecting novel fusion genes and evaluating the role of altered splicing; use of single-cell sequencing to identify heterogeneity of drug response to targeted therapies. For the project we have a unique biobank from a prospective, randomized clinical trial as well as samples from our large AMLSG BiO Registry available.

近年来，下一代测序（NGS）技术的发展极大地提高了我们对AML分子发病机理的理解。但是，大多数关于AML基因组分析的研究来自年轻的成年患者。从老年患者的较小研究中，越来越多的证据表明，老年患者的（EPI）遗传特征与年轻患者的遗传特征大不相同。拟议项目的具体目的是：使用靶向DNA测序至少1,000名年龄较大的AML患者的共突变模式的突变频谱，鉴定共突变模式和相互排他性的鉴定以及对年龄较大AML基因组分类的细化；鉴定用于降压药治疗的预后和预测因素，并建立适用于老年患者的新遗传风险分类；产生表观遗传学特征；转录分析（RNA-SEQ）使用新型的牛津纳米孔技术来检测新型融合基因并​​评估改变剪接的作用；使用单细胞测序来鉴定药物对靶向疗法的反应的异质性。对于该项目，我们提供了来自前瞻性，随机临床试验的独特生物库以及我们大型AMLSG生物注册中心的样品。