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Ex vivo cultures and drug testing of primary acute myeloid leukemia samples: Current techniques and implications for experimental design and outcome
Drug Resistance Updates ( IF 15.8 ) Pub Date : 2020-10-10 , DOI: 10.1016/j.drup.2020.100730
D G J Cucchi 1 , R W J Groen 1 , J J W M Janssen 1 , J Cloos 1
Affiliation  

New treatment options of acute myeloid leukemia (AML) are rapidly emerging. Pre-clinical models such as ex vivo cultures are extensively used towards the development of novel drugs and to study synergistic drug combinations, as well as to discover biomarkers for both drug response and anti-cancer drug resistance. Although these approaches empower efficient investigation of multiple drugs in a multitude of primary AML samples, their translational value and reproducibility are hampered by the lack of standardized methodologies and by culture system-specific behavior of AML cells and chemotherapeutic drugs. Moreover, distinct research questions require specific methods which rely on specific technical knowledge and skills. To address these aspects, we herein review commonly used culture techniques in light of diverse research questions. In addition, culture-dependent effects on drug resistance towards commonly used drugs in the treatment of AML are summarized including several pitfalls that may arise because of culture technique artifacts. The primary aim of the current review is to provide practical guidelines for ex vivo primary AML culture experimental design.



中文翻译:

原发性急性髓系白血病样本的离体培养和药物测试:当前技术和对实验设计和结果的影响

急性髓性白血病 (AML) 的新治疗方案正在迅速出现。临床模型,例如离体培养物被广泛用于开发新药和研究协同药物组合,以及发现药物反应和抗癌药物耐药性的生物标志物。尽管这些方法能够在大量原发 AML 样本中对多种药物进行有效研究,但由于缺乏标准化方法以及 AML 细胞和化疗药物的培养系统特异性行为,它们的转化价值和可重复性受到阻碍。此外,不同的研究问题需要依赖特定技术知识和技能的特定方法。为了解决这些方面,我们在此根据不同的研究问题回顾了常用的培养技术。此外,总结了对 AML 治疗中常用药物耐药性的培养依赖性影响,包括可能由于培养技术伪影而出现的几个陷阱。本次审查的主要目的是为离体原代AML培养实验设计。

更新日期:2020-10-30
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