School of Medicine, Qingdao University, Qingdao, Shandong 266000, P.R. China.
Department of Laboratory Center, Yantai Yuhuangding Hospital Affiliated to Qingdao University Medical College, Yantai, Shandong 264000, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7131-7137. doi: 10.3892/mmr.2017.7486. Epub 2017 Sep 13.
The aim of the present study was to examine the expression and significance of CCAAT/enhancer binding protein α (C/EBPα) and SRY‑related high mobility group box containing transcription factor 4 (SOX4) in chronic myeloid leukemia (CML). Bone marrow samples were collected from patients with CML, and peripheral blood mononuclear cells were collected from healthy controls. Protein and mRNA were extracted from the collected samples, and analyzed using western blotting and reverse transcription‑quantitative polymerase chain reaction analyses, respectively. Spearman's method was used to evaluate the correlation between the expression levels of these two genes, with P<0.05 considered to indicate a statistically significant difference. A total of 79 patients, including 57 patients with newly diagnosed CML and 22 patients treated with imatinib therapy, and 30 controls were enrolled. The expression of SOX4 was upregulated in the patients with CML, whereas the expression of C/EBPα was downregulated (P<0.05). However, no differences were observed among the chronic, accelerated and blastic CML phases, respectively (P>0.05). In addition, no associations were found between the changes in expression and age, gender, white blood cells or the expression of breakpoint cluster region/abelson in patients (P>0.05). However, the expression of SOX4 was negatively correlated with the expression of C/EBPα (P<0.01). Following imatinib treatment, the expression of SOX4 was downregulated in the progression‑free patients, but upregulated in the blastic phase patients, whereas the expression of C/EBPα showed the opposite trend. Therefore, C/EBPα and SOX4 were important and negatively associated with the process of CML, and the C/EBPα‑SOX4 axis may be a novel potential therapeutic target for the treatment of CML.
本研究旨在探讨 CCAAT/增强子结合蛋白α（C/EBPα）和性别决定区 Y 框蛋白 4（SOX4）在慢性髓系白血病（CML）中的表达及意义。收集 CML 患者的骨髓样本和健康对照者的外周血单个核细胞，提取收集样本中的蛋白质和 mRNA，分别采用 Western blot 及逆转录-定量聚合酶链反应分析。采用 Spearman 法评估这两个基因表达水平之间的相关性，以 P<0.05 为差异有统计学意义。共纳入 79 例患者，其中 57 例为初诊 CML 患者，22 例为伊马替尼治疗患者，30 例为健康对照者。结果显示，CML 患者 SOX4 表达上调，C/EBPα 表达下调（P<0.05）。然而，慢性期、加速期和急变期 CML 患者之间的 C/EBPα 表达无差异（P>0.05）。此外，患者的表达变化与年龄、性别、白细胞或 BCR/ABL 表达无相关性（P>0.05）。但是，SOX4 的表达与 C/EBPα 的表达呈负相关（P<0.01）。伊马替尼治疗后，无进展患者的 SOX4 表达下调，急变期患者的 SOX4 表达上调，而 C/EBPα 的表达则呈现相反的趋势。因此，C/EBPα 和 SOX4 是 CML 过程中的重要标志物，与 CML 的发生发展密切相关，C/EBPα-SOX4 轴可能是治疗 CML 的新的潜在治疗靶点。
