加拿大科學(xué)家首度在實驗室老鼠身上，從頭開始培育出人類惡性腫瘤,，讓研究人員能研究癌癥從頭到尾的演變,。
最新一期《科學(xué)》期刊報道，加拿大多倫多大學(xué)分子遺傳系教授,、安大略癌癥研究所資深研究員狄克博士率領(lǐng)的團隊,，以幾個步驟觀察癌癥發(fā)展全程。
第一步,，讓取自人類臍帶血的正常干細胞感染一種會導(dǎo)致血癌的基因,，制造出“人類血癌干細胞”。第二步,，培養(yǎng)基改老鼠,，使之不具免疫系統(tǒng),，也就是不會排斥外來組織。第三步,，將人類血癌干細胞植入老鼠觀察其變化,。
結(jié)果，所有老鼠都出現(xiàn)人類血癌,，亦即其血癌的特征和人類血癌完全相同,。
狄克團隊的空前作法意義非同小可。過去專家就能使老鼠“得癌”,，但那是動物形態(tài)的癌癥,。專家也將人類的癌細胞移植給老鼠，但那是已經(jīng)成形的癌,，無法觀察癌最初是如何發(fā)生的,。
狄克博士表示：“我們真的創(chuàng)造了血癌干細胞。我們眼看著血癌干細胞怎么產(chǎn)生,，如何發(fā)展,，怎么開始不正常，愈來愈不對勁,。”
狄克說,，科學(xué)家看了血癌的整個發(fā)展史，就可以探究一些值得探究的問題：兒童的血癌,，根源是不是可以追溯到胎兒發(fā)育階段,？兒童血癌和成人血癌異同何在？容易發(fā)生血癌的是哪一類型的細胞,？血癌牽涉哪些基因,？
將血癌從孕育到發(fā)展的過程納入掌握，就有希望研發(fā)藥物,，早期制止,。如果使用化療，也會有更精準的目標,。
狄克說,，這種新作法可以協(xié)助科學(xué)家“更了解整體過程，并且更合理的找出關(guān)鍵路徑,，消滅癌癥中最重要的細胞”,。
狄克博士表示，他的團隊目前只做血癌,，但他相信相同的道理應(yīng)該是施之諸“癌”而皆準,，同樣的作法也可以用來觀察其它癌癥。
原始出處:
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
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.
To whom correspondence should be addressed. E-mail: [email protected]
