The Georgia Cancer Center, Augusta University, 1410 Laney Walker Blvd., Augusta, GA 30912, United States.
Genomics. 2019 Dec;111(6):1566-1573. doi: 10.1016/j.ygeno.2018.10.015. Epub 2018 Nov 12.
Constitutive activation of FGFR1 as a result of chromosome translocations is responsible for the development of a hematopoietic stem cell disorder that progresses to AML. We have developed a syngeneic mouse model of BCR-FGFR1 driven AML and used RNASeq to define gene expression signatures associated with disease progression. The development of the leukemic stem cells (LSC) is associated with a profound downregulation of specific transcription factors that normally maintain stem cell quiescence as well as cell adhesion and motility gene sets related to confinement to the stem cell niche. A prominent feature of the LSCs is the upregulation of genes involved in T-cell function, activation, migration and development. Despite this apparent T-cell priming in the LSCs, however, the majority of these genes are subsequently inactivated in the leukemic blast cells that derive from them. These studies provide insights into the molecular etiology of development and progression of FGFR1 driven AML.
由于染色体易位导致的 FGFR1 组成性激活是导致进展为 AML 的造血干细胞疾病的原因。我们已经开发了一种 BCR-FGFR1 驱动的 AML 同基因小鼠模型，并使用 RNASeq 来定义与疾病进展相关的基因表达特征。白血病干细胞 (LSC) 的发展与特定转录因子的显著下调相关，这些转录因子通常维持干细胞静止以及与限制在干细胞龛相关的细胞粘附和运动基因集。LSCs 的一个突出特征是参与 T 细胞功能、激活、迁移和发育的基因上调。然而，尽管 LSCs 中存在这种明显的 T 细胞启动，但大多数这些基因随后在源自它们的白血病母细胞中失活。这些研究为 FGFR1 驱动的 AML 的发展和进展的分子病因提供了深入了解。
