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Tackling Acute Lymphoblastic Leukemia—One Fish at a Time

机译:解决急性淋巴细胞白血病—一次一条鱼

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摘要

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.
机译: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步,但是仍然需要改善策略以降低复发/难治性ALL的发病率并提高治愈率。此类方法包括确定和实施新型靶向组合方案,以及更精确的前期患者风险分层以指导治疗。新的治疗策略依赖对病理生物学的理解,这种理解源于系统地解剖每种癌症的遗传和分子格局。斑马鱼模型提供了一个强大的系统来模拟人类疾病,包括白血病和所有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模型和新型斑马鱼B-ALL模型在翻译ALL中潜在的遗传和分子机制方面所做的贡献,并着重介绍了它们在药物发现中的潜在效用。这些模型为增进我们对ALL分子基础的了解奠定了基础,以进一步寻求改善该重要癌症预后的转化和临床研究工作。

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