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，新一代测序（NGS）技术的发展极大地促进了我们对AML分子发病机制的认识。然而，大多数关于AML基因组谱的研究都来自年轻的成年患者。从老年患者的小型研究中，越来越多的证据表明，老年患者的epi基因谱与年轻患者有很大不同。该项目的具体目标是：在至少1000名老年AML患者的队列中，使用靶向DNA测序评估突变谱，鉴定共突变模式和相互排他性，并改进老年AML的基因组分类；确定低甲基化药物治疗的预后和预测因素，并建立适用于老年患者的新的遗传风险分类；表观遗传特征的产生；转录谱分析（RNA-seq）使用新的牛津纳米孔技术检测新的融合基因和评估剪接改变的作用；使用单细胞测序来确定药物对靶向治疗反应的异质性。对于这个项目，我们有一个来自前瞻性随机临床试验的独特生物库，以及来自我们大型AMLSG生物登记处的样本。