探讨伴正常细胞遗传学的急性髓系白血病患者中 FLT3-ITD 和 NPM1 突变与 Wilms 瘤 1 号外显子 7 突变状态相结合的流行率和预后影响作为潜在的分子生物标志物。

Exploring the Prevalence and Prognostic Impact of Wilms Tumor 1 Exon 7 Mutation Status with Combinations of FLT3-ITD and NPM1 Mutations as Potential Molecular Biomarkers in Acute Myeloid Leukemia Patients with Normal Cytogenetics.

机构信息

Laboratory of Cytogenetics and Molecular Diagnostics, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, University of Kerala, India.

Department of Cancer Research, Laboratory of Cytogenetics and Molecular Diagnostics, Regional Cancer Centre, Thiruvananthapuram, India.

出版信息

Asian Pac J Cancer Prev. 2024 Oct 1;25(10):3463-3470. doi: 10.31557/APJCP.2024.25.10.3463.

DOI:10.31557/APJCP.2024.25.10.3463

PMID:39471012

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11711371/

Abstract

AIM

This study explores the prognostic impact of FLT3-ITD, NPM1, and WT1 mutations both independently and in combination in Cytogenetically Normal Acute Myeloid Leukemia (CN-AML) patients as they exhibit varying clinical outcomes.

METHODS

150 CN-AML patients were selected to assess the prevalence and prognostic significance of WT1 mutations in combination with FLT3-ITD and NPM1 status using polymerase chain reaction (PCR) followed by Sanger sequencing.

RESULTS

WT1 exon 7 mutations were present in 12.6% of patients. Elderly individuals, with a mean age of 49.4 years, were more prone to NPM1 mutations, though the association was not statistically significant (p=0.094). Significant associations were observed between lactate dehydrogenase (LDH) and hemoglobin (Hb) levels with FLT3-ITD and NPM1 mutations (p=0.003 and p=0.04, respectively). The M4 subtype exhibited the highest prevalence of WT1 mutations (p=0.0036). Patients with NPM1 mutations had a higher overall survival rate compared to NPM1 wild-type cases (p=0.057). There was no significant correlation between overall survival and WT1 and FLT3-ITD mutations. Regarding relapse-free survival, NPM1 mutation cases exhibited a higher survival probability compared to NPM1 wild-type cases. Similarly, WT1 mutated cases had a higher survival probability compared to WT1 wild-type cases, although these differences were not statistically significant. The combined mutation statuses of NPM1/FLT3-ITD with WT1 did not yield significant outcomes. The study suggests that larger cohort studies may reveal more relevant associations, given the relatively small cohort in this study.

CONCLUSION

This study found a significant association between patient survival outcomes and NPM1 mutation status, as well as the combined FLT3-ITD and NPM1 status. Profiling both NPM1 and FLT3-ITD mutations at the time of diagnosis serves as a robust prognostic marker in AML treatment. WT1 mutation status did not show a significant association with patient outcomes. Larger population studies may provide more relevant insights.

摘要

目的

本研究旨在探索 FLT3-ITD、NPM1 和 WT1 突变在细胞遗传学正常急性髓系白血病（CN-AML）患者中的独立和联合预后影响，因为它们表现出不同的临床结局。

方法

选择 150 例 CN-AML 患者，采用聚合酶链反应（PCR）结合 Sanger 测序法评估 WT1 突变与 FLT3-ITD 和 NPM1 状态联合的发生率和预后意义。

结果

WT1 外显子 7 突变在 12.6%的患者中存在。年龄较大的患者（平均年龄 49.4 岁）更容易发生 NPM1 突变，但这种关联无统计学意义（p=0.094）。乳酸脱氢酶（LDH）和血红蛋白（Hb）水平与 FLT3-ITD 和 NPM1 突变之间存在显著相关性（p=0.003 和 p=0.04）。M4 亚型 WT1 突变的发生率最高（p=0.0036）。与 NPM1 野生型病例相比，NPM1 突变患者的总生存率更高（p=0.057）。WT1 和 FLT3-ITD 突变与总生存率之间无显著相关性。关于无复发生存率，NPM1 突变病例的生存概率高于 NPM1 野生型病例。同样，WT1 突变病例的生存概率高于 WT1 野生型病例，尽管这些差异无统计学意义。NPM1/FLT3-ITD 与 WT1 的联合突变状态未产生显著结果。该研究表明，鉴于本研究中相对较小的队列，更大的队列研究可能会揭示更多相关关联。