Multi-omics analysis links NFKB1 activation to poor immunosuppressive therapy response in acquired aplastic anemia.

IF 1.6 4区医学 Q3 HEMATOLOGY

Hematology Pub Date : 2025-12-01 Epub Date: 2025-08-13 DOI:10.1080/16078454.2025.2543619

Nianbin Li, Ting Wang, Boyi Wang, Rong Fu

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引用次数: 0

Abstract

Objectives: Acquired aplastic anemia (AA) is a bone marrow failure syndrome whose pathogenesis remains incompletely understood. This study aimed to explore the genetic determinants underlying AA and identify potential therapeutic targets.

Methods: We integrated summary data - based Mendelian randomization (SMR) and colocalization analysis to identify genes causally linked to AA. Key candidates were validated using single-cell RNA sequencing to assess their expression and pseudotime dynamics. We explored B-cell - mediated cell communication related to immunosuppressive therapy response. Serum expression of candidate genes was validated and correlated with clinical outcomes.

Results: SMR analysis identified 28 genes significantly associated with AA, among which NFKB1 emerged as a central regulatory factor. scRNA-seq data confirmed NFKB1's differential expression in B cells and its dynamic regulation during disease progression. Discussion and conclusion: This study is the first to comprehensively characterize the role of NFKB1 in the pathogenesis of AA through integrated multi-omics analysis and providing novel insights for the development of targeted interventions.

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多组学分析将NFKB1激活与获得性再生障碍性贫血免疫抑制治疗反应差联系起来。

目的：获得性再生障碍性贫血（AA）是一种骨髓衰竭综合征，其发病机制尚不完全清楚。本研究旨在探讨AA的遗传决定因素并确定潜在的治疗靶点。方法：我们结合基于汇总数据的孟德尔随机化（SMR）和共定位分析来鉴定与AA相关的基因。使用单细胞RNA测序对关键候选物进行验证，以评估其表达和伪时间动态。我们探讨了与免疫抑制治疗反应相关的b细胞介导的细胞通讯。候选基因的血清表达得到验证，并与临床结果相关。结果：SMR分析鉴定出28个与AA显著相关的基因，其中NFKB1是中心调控因子。scRNA-seq数据证实了NFKB1在B细胞中的差异表达及其在疾病进展过程中的动态调控。讨论与结论：本研究首次通过综合多组学分析全面表征NFKB1在AA发病机制中的作用，为制定针对性干预措施提供新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hematology 医学-血液学

CiteScore

2.60

自引率

5.30%

发文量

140

审稿时长

3 months

期刊介绍： Hematology is an international journal publishing original and review articles in the field of general hematology, including oncology, pathology, biology, clinical research and epidemiology. Of the fixed sections, annotations are accepted on any general or scientific field: technical annotations covering current laboratory practice in general hematology, blood transfusion and clinical trials, and current clinical practice reviews the consensus driven areas of care and management.