Modelling acute myeloid leukemia (AML): What's new? A transition from the classical to the modern.
Modelling acute myeloid leukemia (AML): What's new? A transition from the classical to the modern.
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DOI：
10.1007/s13346-022-01189-4
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发表时间：
2023-08
影响因子：
5.4
通讯作者：
Ryan, Katie B.
中科院分区：
文献类型：
--
作者：
Dozzo, Annachiara;Galvin, Aoife;Shin, Jae-Won;Scalia, Santo;O'Driscoll, Caitriona M.;Ryan, Katie B.
关键词：
急性髓性白血病（AML）是一种影响骨髓（BM）中髓细胞的异质性恶性肿瘤，但可扩散，导致造血功能受损。AML发病率随年龄增长而增加，并与预后不良相关。在血液恶性肿瘤的临床前研究中观察到的新型药物化合物的成功与临床试验中低于特殊的治疗反应之间存在脱节。本综述旨在提供AML不同临床前模型的最新概述，以扩大对疾病病理学的了解并作为临床前筛选工具。解读复杂的生理和病理过程并开发预测性临床前模型是了解疾病进展的关键，也是开发和测试新的有效药物治疗的基础。标准的无支架悬浮模型不能概括AML发生的复杂环境。为此，我们回顾了基于支架/矩阵的3D模型的进展，并概述了芯片技术的最新进展。我们还提供了一个概述临床相关的动物模型和审查扩大使用患者来源的样本，这提供了前景，以创建更多的“患者特异性”的筛选工具，无论是在伪装的3D矩阵模型，微生理“器官芯片”工具或异种移植模型，并讨论代表性的例子。
Acute myeloid leukemia (AML) is a heterogeneous malignancy affecting myeloid cells in the bone marrow (BM) but can spread giving rise to impaired hematopoiesis. AML incidence increases with age and is associated with poor prognostic outcomes. There has been a disconnect between the success of novel drug compounds observed in preclinical studies of hematological malignancy and less than exceptional therapeutic responses in clinical trials. This review aims to provide a state-of-the-art overview on the different preclinical models of AML available to expand insights into disease pathology and as preclinical screening tools. Deciphering the complex physiological and pathological processes and developing predictive preclinical models are key to understanding disease progression and fundamental in the development and testing of new effective drug treatments. Standard scaffold-free suspension models fail to recapitulate the complex environment where AML occurs. To this end, we review advances in scaffold/matrix-based 3D models and outline the most recent advances in on-chip technology. We also provide an overview of clinically relevant animal models and review the expanding use of patient-derived samples, which offer the prospect to create more “patient specific” screening tools either in the guise of 3D matrix models, microphysiological “organ-on-chip” tools or xenograft models and discuss representative examples.
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