Gene expression signatures in childhood acute leukemias are largely unique and distinct from those of normal tissues and other malignancies.
Gene expression signatures in childhood acute leukemias are largely unique and distinct from those of normal tissues and other malignancies.
复制标题
DOI：
10.1186/1755-8794-3-6
复制
发表时间：
2010-03-08
影响因子：
2.7
通讯作者：
Fioretos T
中科院分区：
文献类型：
--
作者：
Andersson A;Edén P;Olofsson T;Fioretos T
儿童白血病的特征是存在平衡的染色体易位或其他结构或数量的染色体变化。众所周知，具有特定分子异常的白血病显示出完全不同的整体基因表达谱。然而，这在很大程度上是未知的，是否这种亚型特异性白血病签名是独特的，或者如果他们也在非造血正常组织或其他人类癌症类型的活性。我们使用基因集富集分析，系统地探讨了儿童急性淋巴细胞白血病（ALL）和髓系白血病（AML）的转录程序是否与正常造血细胞（n = 8），正常非造血组织（n = 22）或人类癌症组织（n = 13）的不同流式分选亚群中的转录程序显著相似。这项研究表明，例如，t（12; 21）ALL的[ETV 6-RUNX 1]亚型和AML的t（15;17）[PML-RARA]亚型分别具有与正常Pro-B细胞和早幼粒细胞相似的转录程序。此外，ALL的11 q23/MLL亚型与非造血组织相似。然而，引人注目的是，其他白血病亚型中的大多数转录程序与来自正常和恶性组织的约100个基因集缺乏显著的相似性。这项研究首次证明，儿童白血病的表达谱在很大程度上是独特的，与正常造血细胞、非造血正常组织或最常见的人类癌症中活跃的转录程序的相似性有限。除了提供重要的发病机制的见解，这些发现应有助于识别候选基因或转录程序，可用作独特的目标，在白血病。
Childhood leukemia is characterized by the presence of balanced chromosomal translocations or by other structural or numerical chromosomal changes. It is well know that leukemias with specific molecular abnormalities display profoundly different global gene expression profiles. However, it is largely unknown whether such subtype-specific leukemic signatures are unique or if they are active also in non-hematopoietic normal tissues or in other human cancer types. Using gene set enrichment analysis, we systematically explored whether the transcriptional programs in childhood acute lymphoblastic leukemia (ALL) and myeloid leukemia (AML) were significantly similar to those in different flow-sorted subpopulations of normal hematopoietic cells (n = 8), normal non-hematopoietic tissues (n = 22) or human cancer tissues (n = 13). This study revealed that e.g., the t(12;21) [ETV6-RUNX1] subtype of ALL and the t(15;17) [PML-RARA] subtype of AML had transcriptional programs similar to those in normal Pro-B cells and promyelocytes, respectively. Moreover, the 11q23/MLL subtype of ALL showed similarities with non-hematopoietic tissues. Strikingly however, most of the transcriptional programs in the other leukemic subtypes lacked significant similarity to ~100 gene sets derived from normal and malignant tissues. This study demonstrates, for the first time, that the expression profiles of childhood leukemia are largely unique, with limited similarities to transcriptional programs active in normal hematopoietic cells, non-hematopoietic normal tissues or the most common forms of human cancer. In addition to providing important pathogenetic insights, these findings should facilitate the identification of candidate genes or transcriptional programs that can be used as unique targets in leukemia.
登录
查看更多内容
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1073/pnas.96.16.9212
发表时间：
1999-08-03
影响因子：
11.1
作者：
Perou, CM;Jeffrey, SS;Botstein, D
通讯作者：
Botstein, D
影响因子：
8
作者：
Rabbitts, TH
通讯作者：
Rabbitts, TH
DOI：
10.1073/pnas.0511150103
发表时间：
2006-02-28
影响因子：
11.1
作者：
Bourquin, JP;Subramanian, A;Orkin, SH
通讯作者：
Orkin, SH
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM