Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, 70124 Bari, Italy.
Int J Mol Sci. 2020 May 13;21(10):3432. doi: 10.3390/ijms21103432.
dysregulation plays a pivotal role in the molecular pathogenesis of myelodysplastic syndromes (MDS), identifying a subgroup of patients with peculiar features. In this review we report the recent biological and clinical findings of -mutated MDS, focusing on the molecular pathways activation and on its impact on the cellular physiology. In MDS, mutational status is deeply associated with del(5q) syndrome and its dysregulation impacts on cell cycle, DNA repair and apoptosis inducing chromosomal instability and the clonal evolution of disease. defects influence adversely the MDS clinical outcome and the treatment response rate, thus new therapeutic approaches are being developed for these patients. allelic state characterization and the mutational burden evaluation can therefore predict prognosis and identify the subgroup of patients eligible for targeted therapy. For these reasons, in the era of precision medicine, the MDS diagnostic workup cannot do without the complete assessment of mutational profile.
失调在骨髓增生异常综合征 (MDS) 的分子发病机制中起着关键作用，确定了一组具有特殊特征的患者。在这篇综述中，我们报告了 -突变 MDS 的最新生物学和临床发现，重点介绍了分子途径的激活及其对细胞生理学的影响。在 MDS 中，突变状态与 del(5q) 综合征密切相关，其失调会影响细胞周期、DNA 修复和凋亡，导致染色体不稳定和疾病的克隆进化。缺陷会对 MDS 的临床结果和治疗反应率产生不利影响，因此正在为这些患者开发新的治疗方法。等位基因状态特征和突变负担评估可以预测预后，并确定适合靶向治疗的患者亚组。因此，在精准医学时代，MDS 的诊断工作不能没有对突变谱的全面评估。
