文章：

SOX4过表达与急性髓系白血病的不良预后相关，并在斑马鱼中具有致白血病作用

Overexpression of SOX4 correlates with poor prognosis of acute myeloid leukemia and is leukemogenic in zebrafish

原文发布日期：2017-08-25

DOI: 10.1038/bcj.2017.74

类型: Original Article

开放获取: 是

英文摘要：

The SOX4 transcription factor is a key regulator of embryonic development, cell-fate decision, cellular differentiation and oncogenesis. Abnormal expression of SOX4 is related to malignant tumor transformation and cancer metastasis. However, no reports are available regarding the clinical significance of SOX4 in acute myeloid leukemia (AML) and the role of SOX4 in leukemogenesis. In the current study, we found that AML patients with low bone marrow (BM) SOX4 expression had higher remission rates and longer overall survival than those with high SOX4 expression, regardless of age, white blood cell count at diagnosis, karyotype profile and NPM1/FLT3-ITD status. To elucidate the role of SOX4 in leukemogenesis, we generated a transgenic zebrafish model that overexpressed human SOX4 in the myeloid lineage Tg(spi1-SOX4-EGFP). These transgenic zebrafish showed, at 5 months of age, increased myelopoiesis with dedifferentiation in kidney marrow. At 9 months of age, their kidney structure was significantly effaced and distorted by increased infiltration of myeloid progenitor cells. These results suggest that SOX4 is not only an independent prognostic factor of AML, but also an important molecular factor in leukemogenesis.

摘要翻译： 

SOX4转录因子是胚胎发育、细胞命运决定、细胞分化和肿瘤发生的关键调控因子。SOX4的异常表达与恶性肿瘤转化及癌症转移相关。然而，目前尚无关于SOX4在急性髓系白血病（AML）中的临床意义及其在白血病发生中作用的报道。本研究发现在当前研究中，我们发现不论年龄、诊断时白细胞计数、核型谱或NPM1/FLT3-ITD状态如何，骨髓SOX4低表达的AML患者比较高表达患者具有更高的缓解率和更长的总生存期。为阐明SOX4在白血病发生中的作用，我们建立了在髓系谱系中过表达人SOX4的转基因斑马鱼模型Tg(spi1-SOX4-EGFP)。这些转基因斑马鱼在5月龄时表现出髓系造血增强伴肾骨髓去分化现象。至9月龄时，其肾脏结构因髓系祖细胞浸润增加而显著消失变形。这些结果表明SOX4不仅是AML的独立预后因素，更是白血病发生的重要分子因子。

原文链接：

Overexpression of SOX4 correlates with poor prognosis of acute myeloid leukemia and is leukemogenic in zebrafish