PDF(Pubmed)
Abstract：
Non-neoplastic bone marrow disorders are main causes of non-regenerative anemia in dogs. Despite the high incidence of the diseases, their molecular pathophysiology has not been elucidated. We previously reported that Miniature Dachshund (MD) was a predisposed breed to be diagnosed with non-neoplastic bone marrow disorders in Japan, and immunosuppressive treatment-resistant MDs showed higher number of platelets and morphological abnormalities in peripheral blood cells. These data implied that treatment-resistant MDs might possess distinct pathophysiological features from treatment-responsive MDs. Therefore, we conducted transcriptomic analysis of bone marrow specimens to investigate the pathophysiology of treatment-resistant MDs. Transcriptomic analysis comparing treatment-resistant MDs and healthy control dogs identified 179 differentially expressed genes (DEGs). Pathway analysis using these DEGs showed that \"Wnt signaling pathway\" was a significantly enriched pathway. We further examined the expression levels of DEGs associated with Wnt signaling pathway and confirmed the upregulation of AXIN2 and CCND2 and the downregulation of SFRP2 in treatment-resistant MDs compared with treatment-responsive MDs and healthy control dogs. This alteration implied the activation of Wnt signaling pathway in treatment-resistant MDs. The activation of Wnt signaling pathway has been reported in human patients with myelodysplastic syndrome (MDS), which is characterized by dysplastic features of blood cells. Therefore, the results of this study implied that treatment-resistant MDs have distinct molecular pathological features from treatment-responsive MDs and the pathophysiology of treatment-resistant MDs might be similar to that of human MDS patients.
摘要：
非肿瘤性骨髓疾病是狗非再生性贫血的主要原因。尽管这些疾病的发病率很高，其分子病理生理学尚未阐明。我们以前报道过，在日本，微型腊肠犬（MD）是一种易患非肿瘤性骨髓疾病的品种，免疫抑制治疗耐药的MD显示出更高的血小板数量和外周血细胞形态异常。这些数据暗示治疗抗性MD可能具有与治疗响应性MD不同的病理生理特征。因此,我们对骨髓标本进行了转录组学分析,以研究耐药MDs的病理生理学.比较治疗抗性MD和健康对照狗的转录组分析鉴定了179个差异表达的基因(DEGs)。使用这些DEGs的通路分析表明“Wnt信号通路”是一个显著富集的通路。我们进一步检查了与Wnt信号通路相关的DEGs的表达水平，并证实了与治疗反应性MD和健康对照犬相比，治疗抗性MD中AXIN2和CCND2的上调以及SFRP2的下调。这种改变暗示了治疗抗性MD中Wnt信号通路的激活。Wnt信号通路的激活在人类骨髓增生异常综合征（MDS）患者中已有报道，其特征是血细胞的发育不良特征。因此,这项研究的结果表明,治疗耐药型MDs与治疗反应型MDs具有不同的分子病理学特征,并且治疗耐药型MDs的病理生理学可能与人类MDS患者相似.
