南方医科大学学报

南方医科大学学报 ›› 2020, Vol. 40 ›› Issue (11): 1601-1606.doi: 10.12122/j.issn.1673-4254.2020.11.10

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RUNX1基因突变对成人急性髓细胞白血病的预后有不良影响

杨艳丽，李甜甜，耿英华，李 骏
  

  • 出版日期:2020-11-20 发布日期:2020-11-23

RUNX1 gene mutations are associated with adverse prognosis of patients with acute myeloidleukemia

  • Online:2020-11-20 Published:2020-11-23

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摘要： 目的 了解Runt相关的转录因子1（RUNX1）在急性髓系白血病（AML）中的突变率及分布情况；探索RUNX1基因突变与临床特征的相关性及其对患者预后的影响。方法 收集158例初发AML患者的骨髓标本，提取骨髓基因组DNA，采用聚合酶链式反应技术（PCR）扩增目的基因片段，应用基因测序分析RUNX1基因突变情况。同时检测ASXL1、DNMT3A、TET2、FLT3、CEBPA、NPM1、IDH2、NRAS及c-KIT突变情况，分析其突变与RUNX1突变的关系。用Kaplan-Meier方法进行生存分析，并行Log-rank检验比较生存时间差异。结果 158例初发急性髓系白血病患者中，共发现RUNX1突变19例，突变率为12.0%，其中A166G 9例，A142T 6例，A162L 4例。RUNX1基因突变组与野生型组的年龄差异有统计学意义（P<0.01），突变组患者年龄偏大，在M4和M5型中的发生率较高，较野生型组更易表达CD36、CD7。RUNX1突变发生于正常核型或预后中等风险核型的患者中，但差异均无统计学意义（P>0.05）。突变组的完全缓解率和生存率均低于野生型组（P<0.05），而两组在性别、初诊时白细胞计数、血红蛋白、血小板计数、骨髓原始细胞比例以及乳酸脱氢酶水平的差异无统计学意义（P>0.05）。结论 RUNX1基因突变对AML患者的预后具有不良影响。

关键词: RUNX1基因, 急性髓系白血病, 基因突变

Abstract: Objective To explore the rate and distribution of Runt- related transcription factor 1 (RUNX1) gene mutations in patients with acute myeloid leukemia (AML) and the correlation of these mutations with the clinical characteristics and survival outcomes of the patients. Methods The genomic DNA extracted from the bone marrow of 158 patients with newly diagnosed AML for PCR amplification of RUNX1 gene and sequence analysis to identify the mutations. The mutations of ASXL1, DNMT3A, TET2, FLT3, CEBPA, NPM1, IDH2, NRAS and c-KIT genes were also examined to analyze their association with RUNX1 gene mutations. Result Among the 158 AML patients, 19 (12.0%) were found to have RUNX1 mutations in A166G (9 cases), A142T (6 cases) and A162L (4 cases). RUNX1 mutations were more frequent in elderly patients (P<0.01) and in cases of AML subtypes M4 and M5, and were associated with more frequent CD36 and CD7 expression as compared with the wild type. RUNX1 mutations were more likely to occur in patients with normal karyotype or karyotypes associated with moderate prognostic risks, but the difference was not significant (P>0.05). The patients with RUNX1 mutations had significantly lower complete remission (CR) rate and overall survival (OS) rate than those without the mutations (P<0.05). RUNX1 mutations were not associated with gender, white blood cell count upon diagnosis, hemoglobin level, platelet count, bone marrow blast cell ratio or lactate dehydrogenase level (P>0.05). Conclusion RUNX1 gene mutations are associated with an adverse prognosis of patients with AML.

Key words: RUNX1 gene, acute myeloid leukemia, gene mutation