Advancements in the molecular pathogenesis of myelodysplastic syndrome
Advancements in the molecular pathogenesis of myelodysplastic syndrome
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DOI：
10.1097/moh.0b013e3283257ac7
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发表时间：
2009-03-01
影响因子：
3.2
通讯作者：
List, Alan F.
中科院分区：
文献类型：
--
作者：
Epling-Burnette, Pearlie K.;List, Alan F.
综述目的骨髓增生异常综合征是一种重要的血液恶性肿瘤，影响不断扩大的老年人口。我们对该疾病生物学的理解受到异质性临床病理特征、难以创建动物模型以及缺乏将分子异常与疾病发病机制联系起来的证据的限制。本综述将讨论骨髓增生异常综合征新进展的重要性。最近的研究结果对骨髓增生异常综合征负担的认识不断提高，人们对开发新的治疗策略和研究这种复杂疾病的分子基础越来越感兴趣。多步骤过程比单一事件更好地解释了骨髓增生异常综合征中观察到的异质性，多种生物力量最终导致端粒侵蚀和基因组不稳定。骨髓祖细胞内的内在遗传因素以及微环境中的外在因素可能会促进克隆选择。在急性髓性白血病转化之前，在这一多步骤途径的关键阶段进行针对性的针对性干预可能会产生最佳的临床结果。总结新发现的分子缺陷、动物模型的创建以及我们对分子发病机制理解的一些进展极大地提高了骨髓增生异常综合征的诊断和治疗潜力。
Purpose of reviewMyelodysplastic syndrome is an important hematological malignancy affecting the expanding aged population. Our understanding of the biology of this disease has been limited by the heterogeneous clinicopathological features, difficulty in creating animal models, and paucity of evidence linking molecular abnormalities to disease pathogenesis. The importance of new advances in myelodysplastic syndrome will be discussed in this review.Recent findingsHeightened awareness of the myelodysplastic syndrome burden has garnered rising interest in the development of new treatment strategies and investigation of the molecular basis of this complex disease. A multistep process explains the heterogeneity observed in myelodysplastic syndrome better than a single event, whereby multiple biological forces culminate in telomere erosion and genomic instability. Intrinsic genetic factors within myeloid progenitors along with extrinsic factors in the microenvironment may foster clonal selection. Specific targeted intervention at critical stages along this multistep pathway, prior to acute myeloid leukemia transformation, may produce the best clinical outcome.SummaryNewly identified molecular defects, the creation of animal models, and several advancements in our understanding of the molecular pathogenesis have dramatically improved diagnostic and therapeutic potential of myelodysplastic syndrome.