Clonal evolution of acute leukemia genomes.
Clonal evolution of acute leukemia genomes.
复制标题
DOI：
10.1038/onc.2012.48
复制
发表时间：
2013-01-10
期刊：
影响因子：
8
通讯作者：
Majeti R
中科院分区：
文献类型：
--
作者：
Jan M;Majeti R
在很大程度上，癌症是由单个细胞谱系中多个突变的积累引起的，这些突变是顺序获得的，并服从于进化过程，在进化过程中，选择驱动更适合的亚克隆的扩展。由于区分和分离不同的癌症亚克隆的技术挑战，这种克隆进化的许多方面都知之甚少，包括个体癌症中不同亚克隆的多样性，导致复发的亚克隆的性质，以及癌前突变的身份。这些问题不仅对我们对癌症生物学的理解很重要，而且在临床上也很重要，因为需要了解导致患者显著发病率和死亡率的难治性和复发性疾病的亚克隆的性质。近年来，先进的基因组技术已被用于研究急性白血病的克隆多样性和进化。儿童急性淋巴细胞白血病（ALL）的研究表明，在个体患者中存在多个白血病起始细胞的遗传亚克隆，具有复杂的克隆结构。对儿科ALL的独立研究也确定，复发的克隆基础是可变的和复杂的，复发经常从克隆祖先进化到主要的新生白血病克隆。在急性淋巴细胞白血病（ALL）和急性髓性白血病（AML）的其他研究中，已经在一些个别病例中发现了白血病前突变。本文将重点介绍这些研究急性白血病基因组克隆进化的最新报道，并讨论其对临床治疗的影响。
In large part, cancer results from the accumulation of multiple mutations in a single cell lineage that are sequentially acquired and subject to an evolutionary process where selection drives the expansion of more fit subclones. Due to the technical challenge of distinguishing and isolating distinct cancer subclones, many aspects of this clonal evolution are poorly understood, including the diversity of different subclones in an individual cancer, the nature of the subclones contributing to relapse, and the identity of pre-cancerous mutations. These issues are not just important to our understanding of cancer biology, but are also clinically important given the need to understand the nature of subclones responsible for the refractory and relapsed disease that cause significant morbidity and mortality in patients. Recently, advanced genomic techniques have been used to investigate clonal diversity and evolution in acute leukemia. Studies of pediatric acute lymphoblastic leukemia (ALL) demonstrated that in individual patients there are multiple genetic subclones of leukemia-initiating cells, with a complex clonal architecture. Separate studies also investigating pediatric ALL determined that the clonal basis of relapse was variable and complex with relapse often evolving from a clone ancestral to the predominant de novo leukemia clone. Additional studies in both ALL and acute myeloid leukemia (AML) have identified pre-leukemic mutations in some individual cases. This review will highlight these recent reports investigating the clonal evolution of acute leukemia genomes and discuss the implications for clinical therapy.
登录
查看更多内容
CD47是人类急性髓样白血病干细胞的不良预后因素和治疗抗体靶标。
影响因子：
64.5
作者：
Majeti R;Chao MP;Alizadeh AA;Pang WW;Jaiswal S;Gibbs KD Jr;van Rooijen N;Weissman IL
通讯作者：
Weissman IL
影响因子：
50.3
作者：
Figueroa ME;Abdel-Wahab O;Lu C;Ward PS;Patel J;Shih A;Li Y;Bhagwat N;Vasanthakumar A;Fernandez HF;Tallman MS;Sun Z;Wolniak K;Peeters JK;Liu W;Choe SE;Fantin VR;Paietta E;Löwenberg B;Licht JD;Godley LA;Delwel R;Valk PJ;Thompson CB;Levine RL;Melnick A
通讯作者：
Melnick A
影响因子：
82.9
作者：
Castor, A;Nilsson, L;Jacobsen, SEW
通讯作者：
Jacobsen, SEW
影响因子：
11.4
作者：
Cloos, J.;Goemans, B. F.;Kaspers, G. J. L.
通讯作者：
Kaspers, G. J. L.
影响因子：
158.5
作者：
Jamieson, CHM;Ailles, LE;Weissman, IL
通讯作者：
Weissman, IL