Jimmy Everest Section of Pediatric Hematology-Oncology, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Int J Mol Sci. 2019 Oct 25;20(21):5313. doi: 10.3390/ijms20215313.
Despite advancements in the diagnosis and treatment of acute lymphoblastic leukemia (ALL), a need for improved strategies to decrease morbidity and improve cure rates in relapsed/refractory ALL still exists. Such approaches include the identification and implementation of novel targeted combination regimens, and more precise upfront patient risk stratification to guide therapy. New curative strategies rely on an understanding of the pathobiology that derives from systematically dissecting each cancer's genetic and molecular landscape. Zebrafish models provide a powerful system to simulate human diseases, including leukemias and ALL specifically. They are also an invaluable tool for genetic manipulation, in vivo studies, and drug discovery. Here, we highlight and summarize contributions made by several zebrafish T-ALL models and newer zebrafish B-ALL models in translating the underlying genetic and molecular mechanisms operative in ALL, and also highlight their potential utility for drug discovery. These models have laid the groundwork for increasing our understanding of the molecular basis of ALL to further translational and clinical research endeavors that seek to improve outcomes in this important cancer.
尽管在急性淋巴细胞白血病（ALL）的诊断和治疗方面取得了进展，但仍需要改进策略来降低复发性/难治性 ALL 的发病率并提高治愈率。这些方法包括确定和实施新的靶向联合方案，以及更精确的 upfront 患者风险分层以指导治疗。新的治疗策略依赖于对源自系统剖析每个癌症的遗传和分子图谱的病理生物学的理解。斑马鱼模型提供了一个强大的系统来模拟人类疾病，包括白血病和 ALL 。它们也是遗传操作、体内研究和药物发现的宝贵工具。在这里，我们重点介绍和总结了几种斑马鱼 T-ALL 模型和更新的斑马鱼 B-ALL 模型在转化 ALL 中起作用的潜在遗传和分子机制方面的贡献，并强调了它们在药物发现方面的潜在应用。这些模型为我们增加对 ALL 分子基础的理解奠定了基础，进一步促进了旨在改善这种重要癌症治疗效果的转化和临床研究工作。
