文章：

一个稳健且快速的异种移植模型，用于评估人类急性髓系白血病化疗药物的疗效

A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia

原文发布日期：2015-03-20

DOI: 10.1038/bcj.2015.19

类型: Original Article

开放获取: 是

英文摘要：

Relevant preclinical mouse models are crucial to screen new therapeutic agents for acute myeloid leukemia (AML). Current in vivo models based on the use of patient samples are not easy to establish and manipulate in the laboratory. Our objective was to develop robust xenograft models of human AML using well-characterized cell lines as a more accessible and faster alternative to those incorporating the use of patient-derived AML cells. Five widely used AML cell lines representing various AML subtypes were transplanted and expanded into highly immunodeficient non-obese diabetic/LtSz-severe combined immunodeficiency IL2Rγcnull mice (for example, cell line-derived xenografts). We show here that bone marrow sublethal conditioning with busulfan or irradiation has equal efficiency for the xenotransplantation of AML cell lines. Although higher number of injected AML cells did not change tumor engraftment in bone marrow and spleen, it significantly reduced the overall survival in mice for all tested AML cell lines. On the basis of AML cell characteristics, these models also exhibited a broad range of overall mouse survival, engraftment, tissue infiltration and aggressiveness. Thus, we have established a robust, rapid and straightforward in vivo model based on engraftment behavior of AML cell lines, all vital prerequisites for testing new therapeutic agents in preclinical studies.

摘要翻译： 

相关的临床前小鼠模型对于筛选急性髓系白血病（AML）的新治疗药物至关重要。目前基于使用患者样本的体内模型在实验室中不易建立和操作。我们的目标是利用特征明确的细胞系开发稳健的人AML异种移植模型，作为使用患者来源AML细胞模型的更易操作且更快速的替代方案。我们将五种代表不同AML亚型的常用AML细胞系移植并扩增到高度免疫缺陷的非肥胖糖尿病/LtSz-重症联合免疫缺陷IL2Rγcnull小鼠中（例如，细胞系来源的异种移植）。我们在此表明，使用白消安或放射进行骨髓亚致死条件处理对于AML细胞系的异种移植具有同等效率。尽管注射更高数量的AML细胞并未改变骨髓和脾脏中的肿瘤移植率，但它显著降低了所有测试AML细胞系小鼠的总生存期。基于AML细胞特性，这些模型还表现出广泛的小鼠总生存期、移植率、组织浸润和侵袭性。因此，我们建立了一个基于AML细胞系移植行为的稳健、快速且直接的体内模型，这些都是临床前研究中测试新治疗药物所必需的关键前提条件。

原文链接：

A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia