Science：利用老鼠培育人类恶性肿瘤观测癌症发展过程

生物谷

    加拿大科学家首度在实验室老鼠身上，从头开始培育出人类恶性肿瘤，让研究人员能研究癌症从头到尾的演变。

    最新一期《科学》期刊报道，加拿大多伦多大学分子遗传系教授、安大略癌症研究所资深研究员狄克博士率领的团队，以几个步骤观察癌症发展全程。

    第一步，让取自人类脐带血的正常干细胞感染一种会导致血癌的基因，制造出“人类血癌干细胞”。第二步，培养基改老鼠，使之不具免疫系统，也就是不会排斥外来组织。第三步，将人类血癌干细胞植入老鼠观察其变化。

    结果，所有老鼠都出现人类血癌，亦即其血癌的特征和人类血癌完全相同。

    狄克团队的空前作法意义非同小可。过去专家就能使老鼠“得癌”，但那是动物形态的癌症。专家也将人类的癌细胞移植给老鼠，但那是已经成形的癌，无法观察癌最初是如何发生的。

    狄克博士表示：“我们真的创造了血癌干细胞。我们眼看着血癌干细胞怎么产生，如何发展，怎么开始不正常，愈来愈不对劲。”

    狄克说，科学家看了血癌的整个发展史，就可以探究一些值得探究的问题：儿童的血癌，根源是不是可以追溯到胎儿发育阶段？儿童血癌和成人血癌异同何在？容易发生血癌的是哪一类型的细胞？血癌牵涉哪些基因？

    将血癌从孕育到发展的过程纳入掌握，就有希望研发药物，早期制止。如果使用化疗，也会有更精准的目标。

    狄克说，这种新作法可以协助科学家“更了解整体过程，并且更合理的找出关键路径，消灭癌症中最重要的细胞”。

    狄克博士表示，他的团队目前只做血癌，但他相信相同的道理应该是施之诸“癌”而皆准，同样的作法也可以用来观察其它癌症。

原始出处:

Science 27 April 2007:
Vol. 316. no. 5824, pp. 600 - 604
DOI: 10.1126/science.1139851

Reports

Modeling the Initiation and Progression of Human Acute Leukemia in Mice

Frédéric Barabé,1,2,3,4* James A. Kennedy,1,5* Kristin J. Hope,1,5 John E. Dick1,5 ${dagger}$

Our understanding of leukemia development and progression has been hampered by the lack of in vivo models in which disease is initiated from primary human hematopoietic cells. We showed that upon transplantation into immunodeficient mice, primitive human hematopoietic cells expressing a mixed-lineage leukemia (MLL) fusion gene generated myeloid or lymphoid acute leukemias, with features that recapitulated human diseases. Analysis of serially transplanted mice revealed that the disease is sustained by leukemia-initiating cells (L-ICs) that have evolved over time from a primitive cell type with a germline immunoglobulin heavy chain (IgH) gene configuration to a cell type containing rearranged IgH genes. The L-ICs retained both myeloid and lymphoid lineage potential and remained responsive to microenvironmental cues. The properties of these cells provide a biological basis for several clinical hallmarks of MLL leukemias.

1 Division of Cell and Molecular Biology, University Health Network, Toronto, Ontario, M5G 1L7, Canada.
2 Department of Medicine, Laval University, Québec, G1K 7P4, Canada.
3 Department of Hematology, Enfant-Jesus Hospital, Qué-bec, G1J 1Z4, Canada.
4 Research Center in Infectious Diseases, Centre Hospitalier Universitaire de Québec–Centre Hospitalier de l'Université Laval, Québec, G1V 4G2, Canada.
5 Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada.

* These authors contributed equally to this work.

${dagger}$ To whom correspondence should be addressed. E-mail: jdick@uhnres.utoronto.ca