Genomic analysis of acute myeloid leukemia: potential for new prognostic indicators.
Genomic analysis of acute myeloid leukemia: potential for new prognostic indicators.
复制标题
DOI：
10.1097/moh.0b013e3283366c43
复制
发表时间：
2010-03
影响因子：
3.2
通讯作者：
Eklund EA
中科院分区：
文献类型：
--
作者：
Eklund EA
急性髓系白血病（AML）是一组异质性克隆性髓系恶性肿瘤。除少数例外，治疗反应并不理想，预后也较差。研究表明，通过经典 G 带识别的特定细胞遗传学异常与预后相关。这些发现提高了预测 AML 结局和调整治疗方案的能力。这些研究还表明，对体细胞基因组突变进行更详细的分析可能会扩展这些进展。包括 DNA 阵列和自动测序在内的新技术改进了对细微的、获得性基因组改变的检测。基于 DNA 阵列的筛选方法可以检测小于 5 兆碱基 (Mb) 的拷贝数改变 (CNA)。亚染色体拷贝数中性杂合性丢失 (CNN-LOH) 也可以利用人类基因组中的单核苷酸多态性 (SNP) 的方法进行检测。然而，白血病克隆中单核苷酸变异（SNV）的鉴定仍然需要靶向或大规模测序方法。最近的研究表明，CNA 和 CNN-LOH 在 AML 中频繁发生。已经确定了可能与疾病发病机制相关的反复出现的异常。然而，需要更大规模的研究来确定这些改变与预后预测或治疗目标的相关性。
Acute myeloid leukemia (AML) is a heterogeneous group of clonal myeloid malignancies. With a few exceptions, response to treatment is unsatisfactory and prognosis is poor. Studies indicate that specific cytogenetic abnormalities, identified by classical G-banding, correlate with prognosis. These findings advanced the ability to predict outcome and to tailor treatments in AML. These studies also suggested that a more detailed analysis of somatic genomic mutations might extend these advances. New technologies, including DNA-arrays and automated sequencing, have improved detection of subtle, acquired genomic alterations. DNA-array based screening approaches permit detection of copy number alterations (CNA) of less than 5 megabase (Mb) in size. Sub-chromosomal copy number neutral loss of heterozygosity (CNN-LOH) can also be detected using approaches that take advantage of single nucleotide polymorphisms (SNPs) in the human genome. However, identification of single nucleotide variants (SNV) in leukemic clones still requires targeted or massive sequencing approaches. Recent studies suggest that CNA and CNN-LOH occur frequently in AML. Recurring abnormalities have been identified which may be relevant to disease pathogenesis. However, larger studies will be required to determine the relevance of these alterations to prognostic prediction or therapeutic targeting.