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人类B细胞前体白血病的基因工程小鼠模型。

Genetically engineered mouse models of human B-cell precursor leukemias.

作者信息

Hauer Julia, Borkhardt Arndt, Sánchez-García Isidro, Cobaleda César

机构信息

a Department of Pediatric Oncology ; Hematology and Clinical Immunology ; Heinrich-Heine University Dusseldorf ; Medical Faculty ; Dusseldorf , Germany.

出版信息

Cell Cycle. 2014;13(18):2836-46. doi: 10.4161/15384101.2014.949137.

Abstract

B-cell precursor acute lymphoblastic leukemias (pB-ALLs) are the most frequent type of malignancies of the childhood, and also affect an important proportion of adult patients. In spite of their apparent homogeneity, pB-ALL comprises a group of diseases very different both clinically and pathologically, and with very diverse outcomes as a consequence of their biology, and underlying molecular alterations. Their understanding (as a prerequisite for their cure) will require a sustained multidisciplinary effort from professionals coming from many different fields. Among all the available tools for pB-ALL research, the use of animal models stands, as of today, as the most powerful approach, not only for the understanding of the origin and evolution of the disease, but also for the development of new therapies. In this review we go over the most relevant (historically, technically or biologically) genetically engineered mouse models (GEMMs) of human pB-ALLs that have been generated over the last 20 years. Our final aim is to outline the most relevant guidelines that should be followed to generate an "ideal" animal model that could become a standard for the study of human pB-ALL leukemia, and which could be shared among research groups and drug development companies in order to unify criteria for studies like drug testing, analysis of the influence of environmental risk factors, or studying the role of both low-penetrance mutations and cancer susceptibility alterations.

摘要

B细胞前体急性淋巴细胞白血病(pB-ALL)是儿童期最常见的恶性肿瘤类型,也影响着相当比例的成年患者。尽管pB-ALL表面上具有同质性,但它包含一组在临床和病理上都非常不同的疾病,由于其生物学特性和潜在的分子改变,其预后也非常多样。要了解它们(作为治愈它们的先决条件)需要来自许多不同领域的专业人员持续进行多学科努力。在所有用于pB-ALL研究的可用工具中,截至目前,使用动物模型是最强大的方法,不仅用于了解疾病的起源和演变,还用于开发新疗法。在这篇综述中,我们回顾了过去20年中生成的人类pB-ALL最相关的(从历史、技术或生物学角度)基因工程小鼠模型(GEMM)。我们的最终目标是概述生成“理想”动物模型应遵循的最相关指南,该模型可成为人类pB-ALL白血病研究的标准,并且可以在研究小组和药物开发公司之间共享,以便统一药物测试、环境危险因素影响分析或研究低 penetrance 突变和癌症易感性改变作用等研究的标准。

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