转录因子SOX4及C／EBPα在慢性粒细胞白血病中的表达及其意义

Expression of transcription factors SOX4 and C/EBPα in chronic myeloid leukemia and their significances

目的研究转录因子SOX4和C／EBPα在慢性粒细胞白血病（CML）患者中的表达水平及其临床意义。方法收集68例CML患者骨髓标本，包括57例初诊患者及11例应用伊马替尼治疗患者，以30名健康体检者的外周血单个核细胞作为健康对照。采用反转录聚合酶链反应（RT-PCR）、Westemblot技术检测SOX4和C／EBPd的表达情况，分析两者表达水平的相关性及应用伊马替尼对二者表达水平的影响。结果与健康对照组相比，SOX4mRNA在初诊CML患者中的表达水平升高（6．5455±1．4952比0．0596±O．0188，t=3．139，P=0．0023），而C／EBP仪表达水平降低（O．2388±0．0338比0．8105±0．0562，t=9．240，P〈0．0001）。两者的表达水平与初诊患者的年龄、性别、白细胞计数和bcr-abl均无相关性（均P〉0．05）。伊马替尼治疗的11例患者中，5例治疗后SOX4表达水平较治疗前降低（0．1206±O．0449比0．5579±0．1448，t=2．885，P=0．0204），C／EBP戏表达水平升高（0．3303±0．0424比0．1505±0．0465，t=2．855，P=0．0213）；6例治疗中发生急变，其SOX4表达水平高于治疗前（0．4699±0．1230比0．0502±0．0366，t=2．370，P=0．0393），C／EBPd表达水平降低（0．19794-0．0647比O．3787±0．0429，t=2．327，P=0．0423）。初诊CML患者SOX4与C／EBP α mRNA的表达水平呈负相关（r=-0．5546，P=0．0028）。结论初诊CML患者中SOX4表达水平明显升高，而C／EBP仅表达水平明显降低，两者表达呈负相关；伊马替尼治疗的急变患者SOX4表达水平比治疗前升高，而C／EBPα比治疗前降低。提示C／EBPd-SOX4信号轴可能参与了CML的发生、发展，且其与预后相关。SOX4为CML的靶向治疗提供了一个新方向。

Objective To investigate the expression of SOX4 and C/EBPα mRNA in chronic myeloid leukemia （CML） and their clinical significances. Methods Bone marrow samples from 68 cases of CML including 57 newly diagnosed patients and 11 patients treated with imatinib were collected, and peripheral blood mononuclear cells from 30 heahhy people were collected as healthy control. The expression of SOX4 and C/EBPα mRNA and protein levels were detected by RT-PCR and Western blot, respectively. The relations between the expression of SOX4 and C/EBPα and the influences of imatinib on SOX4 and C/EBPα were analyzed. Results The expression level of SOX4 mRNA was increased in newly diagnosed CML patients compared with that of normal control group （6.545 5±1.495 2 vs. 0.059 6 ± 0.018 8, t = 3.139, P= 0.002 3）, but the expression level of C/EBPct mRNA was significantly decreased （0.238 8 ± 0.033 8 vs. 0.810 5± 0.056 2, t = 9.240, P〈 0.000 1）. The expression levels of SOX4 and C/EBPα mRNA had no significant correlation with age, gender, white blood cell count （WBC） and bcr-abl of newly diagnosed patients （all P 〉 0.05）. The expression level of SOX4 mRNA in $ patients treated with imatinib was decreased （0.120 6 ± 0.044 9 vs. 0.557 9 ± 0. 144 8, t = 2.885, P= 0.020 4）, and the expression level of C/EBPα mRNA was increased （0.330 3±0.042 4 vs. 0.150 5 ± 0.046 5, t = 2.855, P= 0.021 3）. The expression level of SOX4 mRNA in 6 patients who developed blast phase during the treatment of imatinib was inereased （0.469 9 ±0.123 0 vs. 0.050 2 ±0.036 6, t = 2.370, P=0.039 3）, and the expression level of C/EBPcx mRNA was decreased （0.197 9±0.064 7 vs. 0.378 7 ± 0.042 9, t = 2.327, P = 0.042 3）. The expression of SOX4 mRNA was negatively correlated with C/EBPα mRNA （t =-0.554 6, P= 0.002 8）. Conclusions In newly diagnosed CML, the expression level of SOX4 is increased, C/EBPα is decreased compared with that of healthy control, and both have negative correlation. In the patients in blast phase after imatinib treatment, SOX4 gene is up-regulated, and C/EBPcx is down-regulated. C/EBPcx-SOX4 axis may play a role in the occurrence and development of CML. SOX4 may be a new molecular target for the treatment of CML.