Assessing genetic and epigenetic heterogeneity in hematopoietic neoplasms using single cell genomics (A14)

使用单细胞基因组学评估造血系统肿瘤的遗传和表观遗传异质性 (A14)

• 批准号: 290353298
• 金额: --
• 依托单位: Fach Anthropologie und Humangenetik
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/290353298?language=en
• 关键词: Assessing; genetic; epigenetic; heterogeneity; hematopoietic

Understanding treatment resistance of AML requires to know how fast genetic, epigenetic and transcriptional heterogeneity can evolve. Here, we will use and develop genomic technologies allowing to measure expression, subclonal genotypes and cellular barcodes from single AML cells obtained from series of treated and untreated patient-derived xenograft (PDX) mice. Combined with single-molecule measurements of genetic and epigenetic heterogeneity, this will allow to disentangle molecular levels of clonal evolution and to better model and treat the emergence of resistant AML clones.

了解AML的治疗耐药性需要知道遗传、表观遗传和转录异质性演变的速度有多快。在这里，我们将使用和开发基因组技术，允许测量单个AML细胞的表达、亚克隆基因类型和细胞条形码，这些细胞来自一系列经过治疗和未经治疗的患者来源的异种移植(PDX)小鼠。结合遗传和表观遗传异质性的单分子测量，这将允许解开克隆进化的分子水平，并更好地模拟和治疗耐药AML克隆的出现。