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

了解AML的治疗耐药性需要了解遗传、表观遗传和转录异质性的演变速度。在这里，我们将使用和开发基因组技术，允许测量从一系列治疗和未治疗的患者来源的异种移植（PDX）小鼠获得的单个AML细胞的表达，亚克隆基因型和细胞条形码。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，并更好地建模和治疗耐药AML克隆的出现。

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.