文章：

细胞因子信号传导抑制因子1在急性髓系白血病中的临床生物学意义

Clinico-biological significance of suppressor of cytokine signaling 1 expression in acute myeloid leukemia

原文发布日期：2017-07-28

DOI: 10.1038/bcj.2017.67

类型: Original Article

开放获取: 是

英文摘要：

Suppressor of cytokine signaling 1 (SOCS1) protein, which encodes a member of signal transducers and activators of transcription-induced inhibitors, takes part in a negative regulation of cytokine signaling. The mechanism of SOCS1 in tumor carcinogenesis is complex and there have been no studies concerning the clinic-biologic implication of SOCS1 expression in acute myeloid leukemia (AML). Here, we first identified that higher bone marrow (BM) SOCS1 expression was closely associated with older age, FLT3-ITD, NPM1 and DNMT3A mutations, but negatively correlated with CEBPA mutation in patients with de novo AML. Compared to patients with lower SOCS1 expression, those with higher expression had lower complete remission rates and shorter overall survival. Further, higher expression of SOCS1 in the BM was an independent unfavorable prognostic factor irrespective of age, white blood cell, cytogenetics and gene mutations. Next, we generated zebrafish model overexpressing SOCS1 by spi1 promoter, which showed kidney marrow from adult SOCS1 zebrafish had increased myelopoiesis, myeloid progenitors and the kidney or spleen structure were effaced and distorted, mimicking leukemia phenotype. The SOCS1/FLT3-ITD double transgenic fish could further facilitate the leukemic process. The results indicate SOCS1 plays an important role in AML and its higher expression serves as a new biomarker to risk-stratify AML patients.

摘要翻译： 

细胞因子信号传导抑制蛋白1（SOCS1）作为信号传导及转录激活因子诱导的抑制因子家族成员，参与细胞因子信号的负向调控。SOCS1在肿瘤发生中的作用机制复杂，目前尚无关于SOCS1表达在急性髓系白血病（AML）中临床生物学意义的研究。本研究首次发现，在新诊断AML患者中，较高的骨髓SOCS1表达与高龄、FLT3-ITD、NPM1及DNMT3A突变显著相关，而与CEBPA突变呈负相关。与低表达患者相比，SOCS1高表达患者的完全缓解率更低，总生存期更短。进一步研究发现，无论年龄、白细胞计数、细胞遗传学特征和基因突变状态如何，骨髓SOCS1高表达均是独立的不良预后因素。随后，我们通过spi1启动子构建了SOCS1过表达斑马鱼模型，发现成年SOCS1斑马鱼肾脏骨髓中髓系造血增加、髓系祖细胞增多，肾脏和脾脏组织结构被破坏和扭曲，呈现白血病表型。SOCS1/FLT3-ITD双转基因斑马鱼则进一步加速了白血病进程。这些结果表明SOCS1在AML中发挥重要作用，其高表达可作为AML患者风险分层的新型生物标志物。

原文链接：

Clinico-biological significance of suppressor of cytokine signaling 1 expression in acute myeloid leukemia