Shuai Xiao, Zhou Daobin, Shen Ti, Wu Yongji, Zhang Jieping, Wang Xuan, Li Qian
Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, PR China.
Cancer Genet Cytogenet. 2009 Oct 15;194(2):119-24. doi: 10.1016/j.cancergencyto.2009.06.006.
Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal stem cell diseases with a tendency to progress to leukemic transformation. The cytogenetic and molecular pathogenesis of MDS has not been well understood. SALL4, a newly identified oncogene, modulates stem cell pluripotency and self-renewal capability in embryonic development and also plays a role in leukemogenesis. Overexpression of SALL4 induces MDS-like features and subsequent leukemic progression in transgenic mice. Here, we examined SALL4 expression levels in bone marrow mononuclear cells from MDS patients, acute myeloid leukemia (AML) patients, and normal control subjects using a semiquantitative reverse transcription polymerase chain reaction. Higher levels of SALL4 expression were seen in MDS and AML samples than in control samples. The expression level of SALL4 positively correlated with those of MYC and CCND1, both of which are downstream target genes in the Wnt/beta-catenin pathway. We therefore propose that SALL4 plays a critical role in the pathogenesis of MDS by causing the aberrant activation of the Wnt/beta-catenin pathway.
骨髓增生异常综合征（MDS）是一组异质性克隆性干细胞疾病，有向白血病转化的倾向。MDS的细胞遗传学和分子发病机制尚未完全明确。SALL4是一种新发现的致癌基因，在胚胎发育过程中调节干细胞多能性和自我更新能力，也在白血病发生中起作用。SALL4的过表达在转基因小鼠中诱导出MDS样特征及随后的白血病进展。在此，我们使用半定量逆转录聚合酶链反应检测了MDS患者、急性髓系白血病（AML）患者及正常对照者骨髓单个核细胞中SALL4的表达水平。MDS和AML样本中SALL4的表达水平高于对照样本。SALL4的表达水平与MYC和CCND1的表达水平呈正相关，这两者都是Wnt/β-连环蛋白通路的下游靶基因。因此，我们认为SALL4通过导致Wnt/β-连环蛋白通路的异常激活在MDS的发病机制中起关键作用。
