Baldus Claudia D, Bullinger Lars
Department of Hematology and Oncology, Charité, Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Semin Oncol. 2008 Aug;35(4):356-64. doi: 10.1053/j.seminoncol.2008.04.006.
Acute myeloid leukemia (AML) represents a heterogeneous group of leukemia entities that differ with regard to biology, clinical course, and prognosis. Over the past decades, it has been shown that most AML cases exhibit chromosomal aberrations, gene mutations, and disordered gene expression that alter normal gene function, thereby contributing to leukemic transformation. Especially, in cytogenetically normal AML (CN-AML) molecular genetic and gene expression analyses are becoming of increasing importance. In addition to the impact of gene mutations, including the MLL, FLT3, CEBPA, or NPM1 genes in CN-AML, recent analyses have provided evidence that altered gene expression might not only be of biological but also of prognostic relevance in CN-AML patients. Quantitative reverse-transcriptase polymerase chain reaction (Q-RT-PCR) and recent advances in genome-wide DNA microarray-based gene expression profiling (GEP) represent powerful tools for the systematic exploration of the molecular variation underlying the biologic and clinical heterogeneity of CN-AML. Ultimately, a better understanding of gene expression alterations and hence the molecular basis of the disease will contribute to a refined leukemia classification, which will include both previously known CN-AML subgroups and novel classes defined by distinct gene expression clusters with prognostic significance.
急性髓系白血病（AML）是一组异质性白血病实体，在生物学、临床病程和预后方面存在差异。在过去几十年中，已表明大多数AML病例存在染色体畸变、基因突变和基因表达紊乱，这些改变了正常基因功能，从而促成白血病转化。特别是，在细胞遗传学正常的AML（CN-AML）中，分子遗传学和基因表达分析变得越来越重要。除了基因突变的影响，包括CN-AML中的MLL、FLT3、CEBPA或NPM1基因，最近的分析提供了证据，表明基因表达改变在CN-AML患者中可能不仅具有生物学意义，而且具有预后相关性。定量逆转录聚合酶链反应（Q-RT-PCR）以及基于全基因组DNA微阵列的基因表达谱（GEP）的最新进展，是系统探索CN-AML生物学和临床异质性背后分子变异的有力工具。最终，更好地理解基因表达改变以及疾病的分子基础，将有助于完善白血病分类，其中将包括先前已知的CN-AML亚组以及由具有预后意义的不同基因表达簇定义的新类别。
