干细胞
白血病
髓系白血病
癌症干细胞
生物
造血
癌症研究
基因签名
异种移植
移植
造血干细胞
癌症
基因
基因表达
计算生物学
免疫学
医学
遗传学
内科学
作者
Kolja Eppert,Katsuto Takenaka,Eric R. Lechman,Levi Waldron,Björn Nilsson,Peter van Galen,Klaus H. Metzeler,Armando G. Poeppl,Vicki Ling,Joseph Beyene,Angelo J. Canty,Jayne S. Danska,Stefan K. Bohlander,Christian Buske,Mark D. Minden,Todd R. Golub,Igor Jurišica,Benjamin L. Ebert,John E. Dick
出处
期刊:Nature Medicine
[Springer Nature]
日期:2011-08-28
卷期号:17 (9): 1086-1093
被引量:888
摘要
Xenograft studies indicate that some solid tumors and leukemias are organized as cellular hierarchies sustained by cancer stem cells (CSCs). Despite the promise of the CSC model, its relevance in humans remains uncertain. Here we show that acute myeloid leukemia (AML) follows a CSC model on the basis of sorting multiple populations from each of 16 primary human AML samples and identifying which contain leukemia stem cells (LSCs) using a sensitive xenograft assay. Analysis of gene expression from all functionally validated populations yielded an LSC-specific signature. Similarly, a hematopoietic stem cell (HSC) gene signature was established. Bioinformatic analysis identified a core transcriptional program shared by LSCs and HSCs, revealing the molecular machinery underlying 'stemness' properties. Both stem cell programs were highly significant independent predictors of patient survival and were found in existing prognostic signatures. Thus, determinants of stemness influence the clinical outcome of AML, establishing that LSCs are clinically relevant and not artifacts of xenotransplantation.
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