Potts Kathryn S, Bowman Teresa V
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, United States.
Gottesman Institute for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, NY, United States.
Front Oncol. 2017 Dec 4;7:297. doi: 10.3389/fonc.2017.00297. eCollection 2017.
Human myeloid malignancies represent a substantial disease burden to individuals, with significant morbidity and death. The genetic underpinnings of disease formation and progression remain incompletely understood. Large-scale human population studies have identified a high frequency of potential driver mutations in spliceosomal and epigenetic regulators that contribute to malignancies, such as myelodysplastic syndromes (MDS) and leukemias. The high conservation of cell types and genes between humans and model organisms permits the investigation of the underlying mechanisms of leukemic development and potential therapeutic testing in genetically pliable pre-clinical systems. Due to the many technical advantages, such as large-scale screening, lineage-tracing studies, tumor transplantation, and high-throughput drug screening approaches, zebrafish is emerging as a model system for myeloid malignancies. In this review, we discuss recent advances in MDS and leukemia using the zebrafish model.
人类髓系恶性肿瘤给个体带来了沉重的疾病负担,导致了严重的发病和死亡。疾病形成和进展的遗传基础仍未完全明确。大规模人群研究已发现,剪接体和表观遗传调节因子中存在高频的潜在驱动突变,这些突变会导致恶性肿瘤,如骨髓增生异常综合征(MDS)和白血病。人类与模式生物之间细胞类型和基因的高度保守性,使得在基因可塑性强的临床前系统中研究白血病发生的潜在机制以及进行潜在治疗测试成为可能。由于具有大规模筛选、谱系追踪研究、肿瘤移植和高通量药物筛选方法等诸多技术优势,斑马鱼正成为髓系恶性肿瘤的一种模式系统。在本综述中,我们将讨论利用斑马鱼模型在MDS和白血病研究方面的最新进展。