Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.
Division of Hematology, Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
Blood Cancer J. 2017 Aug 25;7(8):e593. doi: 10.1038/bcj.2017.74.
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.
SOX4 转录因子是胚胎发育、细胞命运决定、细胞分化和癌发生的关键调节因子。SOX4 的异常表达与恶性肿瘤转化和癌症转移有关。然而，目前尚无关于 SOX4 在急性髓系白血病（AML）中的临床意义以及 SOX4 在白血病发生中的作用的报道。在本研究中，我们发现骨髓（BM）中 SOX4 表达水平低的 AML 患者的缓解率和总生存率均高于 SOX4 表达水平高的患者，无论年龄、诊断时的白细胞计数、核型特征和 NPM1/FLT3-ITD 状态如何。为了阐明 SOX4 在白血病发生中的作用，我们构建了一个转基因斑马鱼模型，在髓系谱系 Tg(spi1-SOX4-EGFP)中过表达人 SOX4。这些转基因斑马鱼在 5 个月大时表现出骨髓中髓系细胞分化增加导致的骨髓过度生成，在 9 个月大时，其肾脏结构被大量髓系祖细胞浸润所掩盖和扭曲。这些结果表明，SOX4 不仅是 AML 的独立预后因素，也是白血病发生中的重要分子因素。
