文章：

骨髓增生异常综合征：干细胞疾病的复杂性

Myelodysplastic syndromes: the complexity of stem-cell diseases

原文发布日期：2007-02-01

DOI: 10.1038/nrc2047

类型: Review Article

开放获取: 否

要点：

1. Myelodysplastic syndromes (MDS) comprise the most common malignant blood disorder. MDS are increasing in frequency owing to an ageing population and increased awareness of these diseases.
2. MDS are characterized by ineffective haematopoiesis. The bone marrow cells seem to be abnormal, with dysplastic changes in the nucleus or cytoplasmic granules.
3. MDS can evolve from a refractory anaemia to acute myeloid leukaemia (AML), which is associated with a decrease in intramedullary apoptosis and a block in myeloid differentiation.
4. Previously known as 'preleukaemia' or 'smouldering leukaemia,' MDS can be distinguished from de novo AML through its suppression of normal haematopoiesis, the presence of apoptosis in the early stages of the disease, the presence of chromosome 5 or 7 abnormalities, the incidence of blast cells being less than 20%, normal cellular differentiation at onset, a poorer response to treatment with cytosine arabinoside and an older age at presentation.
5. One of the mysteries of MDS is how the stem cells that give rise to these syndromes differ from that of the AML stem cell. Although there are several genetically-defined mouse models of MDS, MDS stem cells are difficult to engraft in a xenotransplantation model.
6. MDS that arises in paediatric patients might be secondary to inherited bone marrow-failure syndromes (for example, Fanconi anaemia, severe congenital neutropaenia, Shwachman–Diamond syndrome or Diamond–Blackfan anaemia).
7. Most cases of adult MDS are sporadic, but some are due to exposure to genotoxic damage incurred during treatment with chemotherapy or ionizing radiation (therapy-related MDS; tMDS).
8. Allogeneic stem-cell transplant is the only known cure. Newer drug therapies have been directed toward reversing gene silencing by hypomethylating agents (5′-azacitidine or decitabine) or through alteration of the cytokine environment by lenalidomide.

要点翻译：

1. 骨髓增生异常综合征（MDS）是最常见的恶性血液疾病。随着人口老龄化及对该疾病认知度的提升，MDS发病率正持续增长。
2. MDS以无效造血为特征。骨髓细胞呈现异常改变，表现为细胞核或胞质颗粒的发育不良变化。
3. 该疾病可从难治性贫血进展为急性髓系白血病（AML），此过程与骨髓内凋亡减少及髓系分化受阻相关。
4. MDS曾被称为“白血病前期”或“闷燃型白血病”，其与原发性AML的鉴别要点包括：抑制正常造血功能、疾病早期存在凋亡现象、5号或7号染色体异常、原始细胞比例低于20%、起病时细胞分化正常、对阿糖胞苷治疗反应较差及发病年龄较高。
5. MDS的核心谜团之一在于其起源干细胞与AML干细胞的差异。尽管已有多种遗传定义的MDS小鼠模型，但MDS干细胞在异种移植模型中难以成功植活。
6. 儿童MDS可能继发于遗传性骨髓衰竭综合征（如范可尼贫血、严重先天性中性粒细胞减少症、Shwachman-Diamond综合征或Diamond-Blackfan贫血）。
7. 成人MDS多数为散发病例，但部分可因化疗或电离辐射治疗期间遭受基因毒性损伤所致（治疗相关型MDS；t-MDS）。
8. 异基因干细胞移植是当前唯一已知可治愈该病的方法。新型药物治疗策略侧重于通过去甲基化药物（5′-氮杂胞苷或地西他滨）逆转基因沉默，或采用来那度胺改变细胞因子微环境。

英文摘要：

The advent of molecularly targeted drug discovery has facilitated the identification of a new generation of anti-mitotic therapies that target proteins with specific functions in mitosis. The exquisite selectivity for mitosis and the distinct ways in which these new agents interfere with mitosis provides the potential to not only overcome certain limitations of current tubulin-targeted anti-mitotic drugs, but to expand the scope of clinical efficacy that those drugs have established. The development of these new anti-mitotic drugs as targeted therapies faces significant challenges; nevertheless, these potential therapies also serve as unique tools to dissect the molecular mechanisms of the mitotic-checkpoint response.

摘要翻译： 

骨髓增生异常综合征（MDS）患者的患病率正在上升，这是由于人口老龄化和人们对这些疾病的认识不断提高。MDS代表了许多不同的病症，而不仅仅是一种单一疾病，它们通过几种临床特征被归为一类。MDS的一个显著特征是遗传不稳定性，并且相当一部分病例会发展为急性髓系白血病（AML）。我们综述了MDS生物学的三个新兴原则：干细胞功能障碍及其与AML的重叠、遗传不稳定性以及细胞凋亡的失调，这些原则是在遗传性骨髓衰竭综合征、治疗相关MDS和AML的背景下进行讨论的。

原文链接：

Myelodysplastic syndromes: the complexity of stem-cell diseases