急性髓系白血病患者骨髓细胞c-Myc基因的表达及其临床意义

Expression of c-Myc gene and its clinical significance in acute myeloid leukemia

摘要:

目的 研究急性髓系白血病（AML）患者骨髓细胞c-Myc基因的表达及其临床意义。方法 选取2018年9月—2020年9月新疆医科大学第一附属医院143例初治AML患者为研究对象。对照组来自20名志愿者的正常骨髓样本。采用实时荧光定量聚合酶链反应（qRT-PCR）检测AML患者骨髓细胞中c-Myc基因的表达，分析其与临床特征及疗效的关系；采用Sanger测序法检测AML患者C-kit 8/17、NPM1、FLT3-TKD/ITD、CEBPa基因突变情况。影响因素的分析采用单因素Cox和多因素逐步Cox回归模型。结果 初治AML患者的c-Myc基因相对表达量高于对照组（P <0.05）。143例AML患者中基因突变患者98例，检出率为68.5%（98/143）。c-Myc基因表达与CEBPa基因突变呈正相关（r = 0.174，P = 0.037）。c-Myc基因高表达组2个疗程的完全缓解率为40.0%（36/90），c-Myc基因低表达组为77.4%（41/53）。单因素和多因素逐步Cox回归分析结果显示，c-Myc基因高表达和染色体核型分析异常的AML患者有较差的无事件生存和总生存期。结论 c-Myc基因异常表达在AML发病中可能起重要作用，可作为AML疗效和预后的不良分子标志物。

Abstract:

Objective To investigate the expression of the c-Myc gene in bone marrow cells of patients with acute myeloid leukemia (AML) and its clinical significance.Methods We selected 143 newly diagnosed AML patients from the First Affiliated Hospital of Xinjiang Medical University, from September 2018 to September 2020, as the study subjects. A control group consisted of normal bone marrow samples from 20 volunteers. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of the c-Myc gene in AML patient's bone marrow cells and analyze its relationship with clinical characteristics and treatment efficacy. Sanger sequencing was employed to detect mutations in AML patients in C-kit 8/17, NPM1, FLT3-TKD/ITD, and CEBPa genes. The analysis of influencing factors used both single-factor Cox and multiple-factor stepwise Cox regression models.Results The relative expression of the c-Myc gene in newly diagnosed AML patients was higher than that in the control group (P < 0.05). Among the 143 AML patients, 98 had gene mutations, with a detection rate of 68.5% (98/143). The expression of the c-Myc gene was positively correlated with mutations in the CEBPa gene (r = 0.174, P = 0.037). The complete remission rates after two cycles of treatment were 40.0% (36/90) for the high c-Myc gene expression group and 77.4% (41/53) for the low c-Myc gene expression group. Single-factor Cox and multiple-factor stepwise Cox regression analysis results showed that AML patients with high c-Myc gene expression and abnormal chromosomal karyotypes had lower event-free survival and overall survival rates.Conclusion Aberrant expression of the c-Myc gene may play an important role in the pathogenesis of AML and can serve as an adverse molecular marker for AML treatment and prognosis.