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首页> 外文期刊>BMC Medical Genomics >Gene expression signatures in childhood acute leukemias are largely unique and distinct from those of normal tissues and other malignancies
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Gene expression signatures in childhood acute leukemias are largely unique and distinct from those of normal tissues and other malignancies

机译：儿童急性白血病的基因表达特征在很大程度上与正常组织和其他恶性肿瘤不同

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Background 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. Methods 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). Results 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. Conclusions 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.
机译：背景技术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值上的染色体变化。众所周知，具有特定分子异常的白血病显示出截然不同的整体基因表达谱。但是，这种亚型特异性白血病标志是独特的还是在非造血正常组织或其他人类癌症类型中也具有活性，在很大程度上是未知的。方法通过基因集富集分析，我们系统地探讨了儿童急性淋巴细胞白血病（ALL）和髓样白血病（AML）的转录程序是否与正常造血细胞（n = 8），正常的不同流量分类亚群中的转录程序显着相似。非造血组织（n = 22）或人癌组织（n = 13）。结果该研究表明，例如ALL的t（12; 21）[ETV6-RUNX1]亚型和AML的t（15; 17）[PML-RARA]亚型具有与正常Pro-B细胞相似的转录程序和早幼粒细胞。此外，ALL的11q23 / MLL亚型与非造血组织相似。然而，令人惊讶的是，其他白血病亚型中的大多数转录程序与源自正常和恶性组织的〜100个基因集缺乏显着相似性。结论该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，与在正常造血细胞，非造血正常组织或人类最常见形式的癌症中活跃的转录程序的相似性有限。除了提供重要的病原学见解外，这些发现还应有助于鉴定可用作白血病独特靶标的候选基因或转录程序。

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