近日一項(xiàng)新的研究成果表明,，急性骨髓性白血?。ˋML）包含了一種具有干細(xì)胞特性的罕見細(xì)胞,，稱為“白血病干細(xì)胞”,，它比一般的AML細(xì)胞能更好地預(yù)測臨床結(jié)果,。相關(guān)研究成果發(fā)表在最新一期出版的《自然—醫(yī)學(xué)》雜志上,。
癌癥科學(xué)家一直在爭論，一個(gè)腫瘤中所有的細(xì)胞是具有相同作用還是某些癌細(xì)胞更具影響力,，這在過去的10年里一直是實(shí)驗(yàn)?zāi)Ｐ退P(guān)注的重要問題,。以往的異種移植研究也表明，一些實(shí)體瘤和白血病由腫瘤干細(xì)胞（CSCs）所維持的分級(jí)細(xì)胞組成,，但對于腫瘤干細(xì)胞模型與病人的關(guān)系尚未明確,。這是第一次揭示了白血病干細(xì)胞的臨床重要性。
癌癥干細(xì)胞領(lǐng)域的先驅(qū)者約翰·迪克領(lǐng)導(dǎo)的國際研究小組通過對健康的干細(xì)胞,、白血病干細(xì)胞和臨床資料進(jìn)行排序,、分析和比較，發(fā)現(xiàn)白血病干細(xì)胞擁有與正常干細(xì)胞同樣的一組基因或特征,，這可能有助于精準(zhǔn)地預(yù)測患者的病程,。這種干細(xì)胞特征表達(dá)強(qiáng)烈的病人，其剩余的生存時(shí)間比一般的病人會(huì)短些,。
這些干細(xì)胞信號(hào)中的基因提供了一種新的藥物靶點(diǎn),，它能運(yùn)用于消除白血病干細(xì)胞。這些基因同樣顯示了潛在的急性骨髓性白血病的生物標(biāo)記,，能夠用于指導(dǎo)對病人施以更有效的治療,。從長期來看，這一信息還能用于將癌癥治療個(gè)性化,，為病人提供合適的藥物,，而不是用現(xiàn)在放之四海而皆準(zhǔn)的治療方法,，對成群的病人予以同樣的治療。
研究人員表示,，該研究能夠?yàn)閷?shí)體瘤和各種白血病的癌癥干細(xì)胞的臨床重要性的測試提供一個(gè)范例,，推動(dòng)了整個(gè)癌癥干細(xì)胞的研究。(生物谷 Bioon.com）
doi:10.1038/nm.2415
PMC:
PMID:
Stem cell gene expression programs influence clinical outcome in human leukemia
Kolja Eppert; Katsuto Takenaka; Eric R Lechman; Levi Waldron; Björn Nilsson; Peter van Galen; Klaus H Metzeler; Armando Poeppl; Vicki Ling; Joseph Beyene; Angelo J Canty; Jayne S Danska; Stefan K Bohlander; Christian Buske; Mark D Minden; Todd R Golub; Igor Jurisica; Benjamin L Ebert; John E Dick
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.
