Department of Comprehensive Pathology, Tokyo Medical and Dental University, Tokyo, Japan.
Mol Med Rep. 2011 Jul-Aug;4(4):591-6. doi: 10.3892/mmr.2011.493. Epub 2011 May 16.
Myelodysplastic syndromes (MDS) have been defined as a disease entity based on clinical features and morphological findings. Despite similarities in clinical manifestations, genetic abnormalities occurring in hematopoietic cells are heterogeneous among the syndromes. However, recent investigations have revealed that there are common biological events in the bone marrow of MDS cases. Most notably, excessive apoptosis of hematopoietic cells was observed to be induced by the bone marrow microenvironment. The apoptosis was mediated by paracrine as well as autocrine factors, suggesting that medullary stromal and hematopoietic cells play a role in the pathology of disease. Pro-inflammatory cytokines, such as TNFα, in the bone marrow microenvironment are predominantly paracrine mediators of apoptosis. Regarding autocrine stimulation mechanisms, it has recently been shown that the deregulation of ribosomal protein is capable of initiating a stress response in the hematopoietic cell through a p53-mediated signaling pathway. Thus, both the stromal cells of the bone marrow microenvironment and hematopoietic cells themselves possess a common and characteristic biology in this heterogeneous disease entity.
骨髓增生异常综合征（MDS）已被定义为一种基于临床特征和形态学发现的疾病实体。尽管临床表现相似，但发生在造血细胞中的遗传异常在综合征之间是异质的。然而，最近的研究表明，在 MDS 病例的骨髓中存在共同的生物学事件。值得注意的是，观察到造血细胞的过度凋亡是由骨髓微环境诱导的。凋亡是由旁分泌和自分泌因子介导的，这表明骨髓基质细胞和造血细胞在疾病的发病机制中起作用。骨髓微环境中的促炎细胞因子，如 TNFα，主要是凋亡的旁分泌介质。关于自分泌刺激机制，最近已经表明核糖体蛋白的失调能够通过 p53 介导的信号通路在造血细胞中引发应激反应。因此，骨髓微环境中的基质细胞和造血细胞本身在这个异质的疾病实体中具有共同的特征性生物学。
