利用一種新的檢測(cè)方法來研究腫瘤細(xì)胞,，來自美國(guó)加州大學(xué)圣地亞哥分校的研究人員發(fā)現(xiàn)慢性淋巴細(xì)胞白血病(chronic lymphocytic leukemia, CLL)存在克隆進(jìn)化(clonal evolution)的證據(jù)。這種檢測(cè)方法能夠區(qū)分白血病細(xì)胞的特征從而表明這種疾病是侵襲性的還是緩慢性的,，這在人們決定何時(shí)和如何治療病人中發(fā)揮著關(guān)鍵性作用,。相關(guān)研究論文于2012年7月26日在線發(fā)表在Blood期刊上,。
現(xiàn)存的侵襲性或進(jìn)展緩慢的慢性淋巴細(xì)胞白血病(CLL)標(biāo)記物大多數(shù)都是固定的，而且在病人初始被診斷患上CLL之后,，時(shí)間越久，這些標(biāo)記物的預(yù)測(cè)性價(jià)值也隨之下降,。當(dāng)病人的血液樣品被收集時(shí),，這些標(biāo)記物不能可靠地預(yù)測(cè)一名CLL病人是否很快需要接受治療，特別是當(dāng)這名病人被診斷患上CLL多年之后,。
論文通信作者Thomas J. Kipps博士和同事們研究了來自130名有不同程度的風(fēng)險(xiǎn)發(fā)生疾病惡化的CLL病人身上的上千種基因,，特別是那些編碼蛋白的基因。他們鑒定出38個(gè)相互作用基因和蛋白的預(yù)后子網(wǎng)絡(luò),，并且在收集樣品時(shí),，這些子網(wǎng)絡(luò)能夠表明這種疾病的相對(duì)侵襲性和預(yù)測(cè)病人是否需要接受治療。
這些預(yù)后子網(wǎng)絡(luò)提供更好的預(yù)測(cè)性價(jià)值,，這是因?yàn)樗鼈儾⒉皇腔趩蝹€(gè)基因或蛋白的表達(dá)水平,，而是基于它們?nèi)绾蝿?dòng)態(tài)地相互作用和隨著時(shí)間推移如何發(fā)生變化，從而能夠影響CLL和病人癥狀的發(fā)展過程,。
這項(xiàng)研究可能改變科學(xué)家們?nèi)绾嗡伎糃LL和臨床醫(yī)生如何治療這種這種疾?。菏歉玫氐却膊“l(fā)展到后期：腫瘤細(xì)胞更加脆弱和更容易殺死，還是在疾病早期積極地治療緩慢性發(fā)展的腫瘤細(xì)胞：它們的數(shù)量更少但是更難發(fā)現(xiàn)和更加抵抗治療,。(生物谷：Bioon.com)
本文編譯自Tumor cells' inner workings predict cancer progression
doi: 10.1182/blood-2012-03-416461
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Subnetwork-based analysis of chronic lymphocytic leukemia identifies pathways that associate with disease progression
Han-Yu Chuang1, Laura Rassenti2, Michelle Salcedo3, Kate Licon4, Alexander Kohlmann5, Torsten Haferlach6, Robin Foà7, Trey Ideker1, and Thomas J. Kipps
The clinical course of patients with chronic lymphocytic leukemia (CLL) is heterogeneous. Several prognostic factors have been identified that can stratify patients into groups that differ in their relative tendency for disease progression and/or survival. Here, we pursued a subnetwork-based analysis of gene expression profiles to discriminate between groups of patients with disparate risks for CLL progression. From an initial cohort of 130 patients, we identified 38 prognostic subnetworks that could predict the relative risk for disease progression requiring therapy from the time of sample collection, more accurately than established markers. The prognostic power of these subnetworks then was validated on two other cohorts of patients. We noted reduced divergence in gene expression between leukemia cells of CLL patients classified at diagnosis with aggressive versus indolent disease over time. The predictive subnetworks vary in levels of expression over time but exhibit increased similarity at later time points prior to therapy, suggesting that degenerate pathways apparently converge into common pathways that are associated with disease progression. As such, these results have implications for understanding cancer evolution and for the development of novel treatment strategies for patients with CLL.
