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携带三重突变的急性髓系白血病患者的临床特征与预后及……的潜在预后价值

Clinical Characteristics and Outcomes of Acute Myeloid Leukemia Patients Harboring Triple Mutations and the Potential Prognostic Value of .

作者信息

Niu Yujie, Luo Xingchun, Yang Xiaoxiao, Guo Yuancheng, Tang Xiao, Zhao Long, Jian Jinli, Liu Bei

机构信息

The First Clinical Medical School, Lanzhou University, Lanzhou, China.

Department of Hematology, Xi'an Central Hospital, Xi'an, China.

出版信息

Cancer Control. 2025 Jan-Dec;32:10732748251359836. doi: 10.1177/10732748251359836. Epub 2025 Jul 17.

DOI:10.1177/10732748251359836
PMID:40676766
Abstract

IntroductionNucleophosmin 1 (), FMS-like tyrosine kinase 3-internal tandem duplication (), and de novo methyl transferase 3 A () triple-mutated acute myeloid leukemia (AML) represents a distinct entity with poor outcomes.MethodsWe explored the gene mutation spectrum and clinical characteristics of 165 AML patients retrospectively, particularly comparing patients with triple-mutations and those without.ResultsOur results demonstrated significantly elevated white blood cell counts ( < 0.001), bone marrow blast percentages ( = 0.037), and platelet counts ( = 0.007) in the triple-mutated cohort (6.7%) compared to the non-triple-mutated patients. Furthermore, all triple-mutated cases were classified as the M4/M5 subtype of the French-American-British classification ( = 0.017). Although no significant difference in complete remission rates was observed between the groups after initial treatment, the median overall survival for triple-mutated AML patients was only 4 months. Using the Gene Expression Omnibus (GEO) database and bioinformatics, we compared AML and AML. A total of 246 AML patients from the GEO dataset were included to evaluate the expression profiles of differentially expressed genes. The guanine nucleotide-binding protein subunit γ 4 () was differentially expressed between AML and AML, which had the most adjacent nodes among hub genes. The prognostic value of was further validated in AML patient samples through qRT-PCR.ConclusionClinical validation indicated a substantial downregulation of in AML compared to AML patients. Thus, may play a role in the low survival rate of AML patients, offering novel insights into the prognosis, therapeutic targets, and prognostic evaluation of AML.

摘要

引言

核磷蛋白1(NPM1)、FMS样酪氨酸激酶3内部串联重复突变(FLT3-ITD)和从头甲基转移酶3A(DNMT3A)三基因突变的急性髓系白血病(AML)是一种预后较差的独特疾病实体。

方法

我们回顾性研究了165例AML患者的基因突变谱和临床特征,特别比较了三基因突变患者和非三基因突变患者。

结果

我们的结果显示,与非三基因突变患者相比,三基因突变队列(6.7%)中的白细胞计数(P<0.001)、骨髓原始细胞百分比(P = 0.037)和血小板计数(P = 0.007)显著升高。此外,所有三基因突变病例均被归类为法国-美国-英国分类法中的M4/M5亚型(P = 0.017)。虽然初始治疗后两组之间的完全缓解率没有显著差异,但三基因突变AML患者的中位总生存期仅为4个月。我们使用基因表达综合数据库(GEO)和生物信息学比较了NPM1突变型AML和野生型AML。总共纳入了来自GEO数据集的246例AML患者,以评估差异表达基因的表达谱。鸟嘌呤核苷酸结合蛋白亚基γ4(GNG4)在NPM1突变型AML和野生型AML之间存在差异表达,它在枢纽基因中具有最多的相邻节点。通过qRT-PCR在AML患者样本中进一步验证了GNG4的预后价值。

结论

临床验证表明,与野生型AML患者相比,NPM1突变型AML中GNG4显著下调。因此,GNG4可能在AML患者低生存率中发挥作用,为AML的预后、治疗靶点和预后评估提供了新的见解。

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