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成年近交 MHC 定义的小型猪的骨髓性白血病:人类髓系白血病的模型

Myelogenous leukemia in adult inbred MHC-defined miniature swine: a model for human myeloid leukemias.

作者信息

Duran-Struuck Raimon, Cho Patricia S, Teague Alexander G S, Fishman Brian, Fishman Aaron S, Hanekamp John S, Moran Shannon G, Wikiel Krzysztof J, Ferguson Kelly K, Lo Diana P, Duggan Michael, Arn J Scott, Billiter Bob, Horner Ben, Houser Stuart, Yeap Beow Yong, Westmoreland Susan V, Spitzer Thomas R, McMorrow Isabel M, Sachs David H, Bronson Roderick T, Huang Christene A

机构信息

Transplantation Biology Research Center, Massachusetts General Hospital, United States.

出版信息

Vet Immunol Immunopathol. 2010 Jun 15;135(3-4):243-56. doi: 10.1016/j.vetimm.2009.12.005. Epub 2009 Dec 29.

Abstract

This manuscript reports on five cases of spontaneous myelogenous leukemia, similar to human disease, occurring within highly inbred, histocompatible sublines of Massachusetts General Hospital (MGH) MHC-defined miniature swine. In cases where a neoplasm was suspected based on clinical observations, samples were obtained for complete blood count, peripheral blood smear, and flow cytometric analysis. Animals confirmed to have neoplasms were euthanized and underwent necropsy. Histological samples were obtained from abnormal tissues and suspect lesions. The phenotype of the malignancies was assessed by flow cytometric analysis of processed peripheral blood mononuclear cells and affected tissues. Five cases of spontaneous myeloid leukemia were identified in adult animals older than 30 months of age. All animals presented with symptoms of weight loss, lethargy, and marked leukocytosis. At autopsy, all animals had systemic disease involvement and presented with severe hepatosplenomegaly. Three of the five myelogenous leukemias have successfully been expanded in vitro. The clustered incidence of disease in this closed herd suggests that genetic factors may be contributing to disease development. Myelogenous leukemia cell lines established from inbred sublines of MGH MHC-defined miniature swine have the potential to be utilized as a model to evaluate therapies of human leukemia.

摘要

本手稿报告了5例自发性骨髓性白血病病例,这些病例与人类疾病相似,发生在麻省总医院(MGH)MHC定义的近交、组织相容性亚系微型猪中。在根据临床观察怀疑有肿瘤的病例中,采集样本进行全血细胞计数、外周血涂片和流式细胞术分析。确诊患有肿瘤的动物实施安乐死并进行尸检。从异常组织和可疑病变处获取组织学样本。通过对处理后的外周血单核细胞和受影响组织进行流式细胞术分析来评估恶性肿瘤的表型。在30个月龄以上的成年动物中鉴定出5例自发性髓细胞白血病病例。所有动物均出现体重减轻、嗜睡和明显白细胞增多的症状。尸检时,所有动物均有全身疾病累及,并出现严重的肝脾肿大。5例骨髓性白血病中有3例已成功在体外扩增。这种封闭猪群中疾病的聚集性发病表明遗传因素可能在疾病发展中起作用。从MGH MHC定义的微型猪近交亚系建立的骨髓性白血病细胞系有潜力用作评估人类白血病治疗方法的模型。

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