Anaplastic large cell lymphoma-propagating cells are detectable by side population analysis and possess an expression profile reflective of a primitive origin

Moti N.; Malcolm T.; Hamoudi R.Mian S.Garland G.Hook C. E.Burke G. A. A.Wasik M. A.Merkel O.Kenner L.Laurenti E.Dick J. E.Turner S. D.

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Anaplastic large cell lymphoma-propagating cells are detectable by side population analysis and possess an expression profile reflective of a primitive origin

机译：间变性大细胞淋巴瘤增殖细胞可通过侧群分析检测到，并具有反映原始起源的表达谱

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Cancer stem cells or tumour-propagating cells (TPCs) have been identified for a number of cancers, but data pertaining to their existence in lymphoma so far remain elusive. We show for the first time that a small subset of cells purified from human anaplastic lymphoma kinase (ALK)-positive and -negative, anaplastic large cell lymphoma cell lines and primary patient tumours using the side population (SP) technique have serial tumour-propagating capacity both in vitro and in vivo; they give rise to both themselves and the bulk tumour population as well as supporting growth of the latter through the production of soluble factors. In vivo serial dilution assays utilising a variety of model systems inclusive of human cell lines, primary human tumours and nucleophosmin (NPM)-ALK-induced murine tumours demonstrate the TPC frequency to vary from as many as 1/54 to 1/1336 tumour cells. In addition, the SP cells express higher levels of pluripotency-associated transcription factors and are enriched for a gene expression profile consistent with early thymic progenitors. Finally, our data show that the SP cells express higher levels of the NPM-ALK oncogene and are sensitive to an ALK inhibitor.

机译：癌症干细胞或肿瘤增殖细胞（TPC）已被确定用于许多癌症，但迄今为止，有关它们在淋巴瘤中存在的数据仍然难以捉摸。我们首次表明，使用侧群（SP）技术从人间变性淋巴瘤激酶（ALK）阳性和阴性、间变性大细胞淋巴瘤细胞系和原发性患者肿瘤中纯化的一小部分细胞在体外和体内都具有连续肿瘤传播能力;它们既产生自身，又产生大量肿瘤种群，并通过产生可溶性因子来支持后者的生长。利用各种模型系统（包括人类细胞系、原发性人类肿瘤和核磷蛋白（NPM）-ALK 诱导的小鼠肿瘤）的体内连续稀释测定表明 TPC 频率从多达 1/54 到 1/1336 个肿瘤细胞不等。此外，SP细胞表达更高水平的多能性相关转录因子，并富集与早期胸腺祖细胞一致的基因表达谱。最后，我们的数据表明，SP细胞表达更高水平的NPM-ALK癌基因，并且对ALK抑制剂敏感。

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《Oncogene》 |2015年第14期|1843-1852|共10页
作者
Moti N.; Malcolm T.; Hamoudi R.Mian S.Garland G.Hook C. E.Burke G. A. A.Wasik M. A.Merkel O.Kenner L.Laurenti E.Dick J. E.Turner S. D.;
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Univ Cambridge, Div Mol Histopathol, Dept Pathol, Cambridge CB2 0QQ, England;

Univ Hail, Coll Appl Med Sci, Mol Diagnost & Personalised Therapeut Unit, Hail, Saudi Arabia;

Addenbrookes Hosp, Dept Histopathol & Cytol, Cambridge, EnglandAddenbrookes Hosp, Dept Paediat Oncol, Cambridge, EnglandUniv Penn, Dept Pathol & Lab Med, Philadelphia, PA USAGerman Canc Res Ctr, Dept Translat Oncol, Natl Ctr Tumor Dis NCT, Heidelberg, GermanyMed Univ Vienna, European Res Initiat ALK Related Malignancies ERI, Vienna, AustriaUniv Hlth Network, Princess Margaret Hosp, Ontario Canc Inst, Campbell Family Inst, Toronto, ON;

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正文语种英语
中图分类肿瘤学;
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Anaplastic large cell lymphoma-propagating cells are detectable by side population analysis and possess an expression profile reflective of a primitive origin

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