γ-catenin基因在急性髓系白血病患者骨髓细胞中的表达及临床意义

Expression and clinical significance of γ-catenin gene in bone marrow cells from patients with acute myeloid leukemia

    摘要
  • 摘要:
    目的 探讨γ-catenin在急性髓系白血病（acute myeloid leukemia，AML）患者骨髓中的表达水平及对临床疗效及预后的影响。
    方法 采用qRT-PCR方法检测新疆医科大学第一附属医院2020年8月至2022年8月的142例初诊AML患者及20例对照样本骨髓中γ-catenin基因表达量；应用Sanger测序法检测NPM1、FLT3-ITD/TKD、C-KIT8/17、DNMT3A及CEBPα/β基因突变情况。
    结果 142例初诊AML患者的γ-catenin基因相对表达量明显高于对照组2.32（0.12～23.64）vs. 0.59（0.12～1.45），（Z=−4.404，P<0.001）。依据AML患者细胞遗传学改变进行危险度分级发现，γ-catenin基因表达量与细胞遗传学危险度呈正相关（r=0.235，P=0.005），并发现高危细胞遗传学（high-risk cytogenetics，HRC）组的γ-catenin基因表达水平明显高于标危细胞遗传学（standard-risk cytogenetics，SRC）组及中危细胞遗传学（medium-risk cytogenetics，MRC）组。初诊AML患者的基因突变检出率为56.34%，γ-catenin基因表达量与NPM1基因突变呈负相关（r=−0.169，P=0.045），与CEBPα/β单基因突变呈正相关（r=0.173，P=0.040）。γ-catenin基因的表达水平与完全缓解率（complete response，CR）呈负相关（r =−0.257，P=0.002）。γ-catenin基因低表达组较高表达组有更长的无事件生存期（event-free survival，EFS）（P=0.002）和总生存期（overall survival，OS）（P=0.003），HRC组的OS明显短于MRC组（P=0.012）。Cox模型单因素及多因素分析均显示γ-catenin基因高表达是AML患者EFS的重要影响因素，γ-catenin基因高表达以及细胞遗传学改变是AML患者OS的重要影响因素。
    结论 γ-catenin基因表达异常可能是参与AML疾病进程的重要分子事件之一，监测其表达水平的变化有助于AML诊断及治疗策略优化。

     

    Abstract:
    Objective To investigate γ-catenin expression in the bone marrow of patients with acute myeloid leukemia (AML) and its impact on clinical outcomes and prognosis.
    Methods Reverse transcription-quantitative polymerase chain reaction (qRT-PCR) was used to evaluate γ-catenin gene expression in the bone marrow of 142 patients with AML and 20 control individuals. Sanger gene sequencing was used to detect mutations in NPM1, FLT3-ITD/TKD, C-KIT8/17, DNMT3A, and CEBPα/β.
    Results The relative expression level of γ-catenin in 142 patients with newly diagnosed AML was significantly higher than that in the control group 2.32 (0.12–23.64) vs. 0.59 (0.12–1.45), (Z=−4.404, P<0.005). In patients with AML, γ-catenin gene expression was positively correlated with cytogenetic risk (r=0.235, P=0.005) and was significantly higher in the high-risk cytogenetics (HRC) group than in the standard-risk cytogenetics (SRC) group and the medium-risk cytogenetics (MRC) group. The mutation detection rate in patients with newly diagnosed AML was 56.34%. γ-catenin gene expression was negatively correlated with NPM1 gene mutations (r=−0.169, P=0.045) and positively correlated with the single gene mutation of CEBPα/β (r=0.173, P=0.040). Moreover, it was negatively correlated with the complete response rate (r=−0.257, P=0.002). Compared with the high-expression group, the low-expression group had a significantly longer event-free survival (EFS; P=0.002) and overall survival (OS; P=0.003), and the OS of the HRC group was significantly shorter than that of the MRC group (P=0.012). Univariate and multivariate Cox analyses showed thatin patients with AML, high γ-catenin gene expression was an independent predictor of EFS, where as high γ-catenin gene expression and cytogenetic abnormalities were independent predictors of OS.
    Conclusions Aberrant γ-catenin gene expression may be an important molecular eventin AML pathogenesis. Monitoring changes in γ-catenin gene expression levels may facilitate the diagnosis and optimization of treatment strategies for AML.

     

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