Barańska Marta, Czerwińska-Rybak Joanna, Gil Lidia, Komarnicki Mieczysław
Chair and Department of Hematology and Bone Marrow Transplantology.
Pol Merkur Lekarski. 2015 Jan;38(223):5-10.
The myelodysplastic syndromes (MDS) constitute heterogeneous group of clonal disorders, characterized by ineffective hematopoiesis, peripheral cytopenia and increased risk of acute myeloid leukemia development. Molecular mechanisms behind MDS have not been fully explained, however recent studies based on new technologies confirmed that epigenetic abnormalities and somatic mutation in the spliceasome machinery are crucial in pathogenesis of these diseases. Abnormal mRNA splicing (excision of intronic sequences from mRNA) has been found in over half of all MDS patients and resulted in accumulation of cytogenetical and molecular changes. The biological impact of splicing factor genes mutations has been evaluated only in a limited extend and current studies concentrate on analysis of MDS transcriptome. Molecular characteristic of classical and alternative splicing is presented in the paper, according to current knowledge. We review the most prominent findings from recent years concerning mutation in the spliceasome machinery with respect to MDS phenotype and disease prognosis. Perspectives in applying of novel diagnostic and therapeutic possibilities for myelodysplasia, based on spliceosome mutations identification are also presented.
骨髓增生异常综合征（MDS）是一组异质性克隆性疾病，其特征为造血无效、外周血细胞减少以及急性髓系白血病发生风险增加。MDS背后的分子机制尚未完全阐明，然而基于新技术的近期研究证实，表观遗传异常和剪接体机制中的体细胞突变在这些疾病的发病机制中至关重要。超过半数的MDS患者存在异常mRNA剪接（从mRNA中切除内含子序列），并导致细胞遗传学和分子改变的积累。剪接因子基因突变的生物学影响仅在有限程度上得到评估，目前的研究集中在MDS转录组分析。根据目前的知识，本文介绍了经典剪接和可变剪接的分子特征。我们回顾了近年来关于剪接体机制突变与MDS表型和疾病预后相关的最突出发现。还介绍了基于剪接体突变识别在骨髓增生异常方面应用新型诊断和治疗方法的前景。
