Macedo Luciana Conci, Silvestre Ana Paula Avenia, Rodrigues Camila, de Alencar Josiane Bazzo, Zacarias Joana Maira Valentini, Ambrosio-Albuquerque Eliane Papa, Sell Ana Maria, Visentainer Jeane Eliete Laguila
Sciences Basic Health Department, State University of Maringa, Maringa, PR, Brazil.
Biotechnology, Genetics and Cellular Biology Department, State University of Maringa, Maringa, PR, Brazil.
Blood Cells Mol Dis. 2015 Jun;55(1):76-81. doi: 10.1016/j.bcmd.2015.04.003. Epub 2015 Apr 17.
The myelodysplastic syndromes (MDS) are a clinically and cytogenetically heterogeneous group of clonal diseases. Clonal chromosomal abnormalities are observed in 30-50% of patients with MDS. The deletions are among the most common alterations, and often involve the long arms of chromosomes 5, 7, 8, 13, and 20 and the short arms of chromosomes 12 and 17. The advent of new technologies for the detection of genetic abnormalities led to the description of a new set of recurrent mutations, leading to new insights into the pathophysiology of MDS. The recent recognition that genes involved in the regulation of histone function (EZH2, ASXL1, and UTX) and DNA methylation (DNMT3A, IDH1/IDH2, and TET2) are frequently mutated in MDS, has led to the proposal that there is an important link between genetic and epigenetic alterations in this disease. In fact, regulatory factors have also been considered as miR-143/miR-145, miR-146a, miR-125a and MiR-21. Somatic mutations may influence the clinical phenotype but are not included in current prognostic scoring systems. In recent years research has brought new insights into these diseases, but few of the findings are sufficiently robust to be incorporated into the clinical routine at this time. Thus, the aim of this study was to review the role of genetic factors involved in the diagnosis and development of the different phenotypes of MDS.
骨髓增生异常综合征（MDS）是一组临床和细胞遗传学表现均异质性的克隆性疾病。30% - 50%的MDS患者存在克隆性染色体异常。缺失是最常见的改变之一，常累及5号、7号、8号、13号和20号染色体长臂以及12号和17号染色体短臂。检测遗传异常的新技术的出现，使得一系列新的复发性突变得以描述，从而为MDS的病理生理学带来了新的见解。最近认识到，参与组蛋白功能调控（EZH2、ASXL1和UTX）以及DNA甲基化（DNMT3A、IDH1/IDH2和TET2）的基因在MDS中经常发生突变，这使得人们提出在这种疾病中，遗传和表观遗传改变之间存在重要联系。事实上，调控因子还包括miR - 143/miR - 145、miR - 146a、miR - 125a和MiR - 21。体细胞突变可能影响临床表型，但未纳入当前的预后评分系统。近年来的研究为这些疾病带来了新的见解，但目前很少有研究结果足够可靠，可以纳入临床常规。因此，本研究的目的是综述遗传因素在MDS不同表型的诊断和发展中的作用。
