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BAALC 基因表达在成人 NPM1 野生型/FLT3-ITD 阴性细胞遗传学正常急性髓系白血病中诉说着严重的患者预后故事。

BAALC gene expression tells a serious patient outcome tale in NPM1-wild type/FLT3-ITD negative cytogenetically normal-acute myeloid leukemia in adults.

机构信息

Laboratory Oncology, AIIMS, New Delhi, India.

Pulmonary Medicine, AIIMS, New Delhi, India.

出版信息

Blood Cells Mol Dis. 2022 Jul;95:102662. doi: 10.1016/j.bcmd.2022.102662. Epub 2022 Apr 8.

Abstract

Acute myeloid leukemia with normal cytogenetics (CN-AML) is the largest group of AML patients which is associated with a variegated patient outcome. Multiple molecular markers have been used to risk-stratify these patients. Estimation of expression of BAALC gene (Brain and Acute Leukemia, Cytoplasmic) mRNA level is one of the predictive markers which has been identified in multiple studies. In this study, we examined the clinical and prognostic value of BAALC gene expression in 149 adult CN-AML patients. We also utilized multi-omics databases to ascertain the association of BAALC gene expression with comprehensive molecular and clinicopathologic features in AML. BAALC overexpression was associated with CD34 positivity on leukemic blasts (p = 0.0026) and the absence of NPM1 gene mutation (p < 0.0001), presence of RUNX1 gene mutation (p < 0.001) and poor patient outcomes, particularly in NPM1-wild type/FLT3-ITD negative adult CN-AML patients. Additionally, BAALC expression was associated with the alteration of methylation of its promoter. Further, pathway analysis revealed that BAALC expression is correlated with MYC targets and Ras signalling. We conclude that high BAALC expression associates with poor patient outcome in NPM1-wild type/FLT3-ITD negative adult CN-AML patients.

摘要

伴有正常细胞遗传学的急性髓系白血病(CN-AML)是 AML 患者中最大的一组,与患者预后的多样性相关。已经使用了多种分子标志物来对这些患者进行风险分层。BAALC 基因(脑和急性白血病,细胞质)mRNA 水平的表达估计是已在多项研究中确定的预测标志物之一。在这项研究中,我们检查了 149 例成人 CN-AML 患者中 BAALC 基因表达的临床和预后价值。我们还利用多组学数据库来确定 BAALC 基因表达与 AML 中综合分子和临床病理特征的关联。BAALC 过表达与白血病细胞上 CD34 阳性(p=0.0026)和 NPM1 基因突变缺失(p<0.0001)、RUNX1 基因突变存在(p<0.001)以及不良患者预后相关,尤其是在 NPM1 野生型/FLT3-ITD 阴性的成人 CN-AML 患者中。此外,BAALC 表达与启动子甲基化的改变有关。此外,途径分析表明,BAALC 表达与 MYC 靶标和 Ras 信号相关。我们得出结论,高 BAALC 表达与 NPM1 野生型/FLT3-ITD 阴性的成人 CN-AML 患者的不良预后相关。

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