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Background <p>Cytogenetically normal acute myeloid leukemia (CN-AML), the most heterogeneous subgroup, requires molecular markers for effective management. Recent studies have highlighted abnormal lipid metabolism as a critical feature driving AML progression, and Sterol Regulatory Element-Binding Factor 2 (<i>SREBF2</i>) – a key regulator of cholesterol metabolism – orchestrates this process by controlling genes involved in sterol biosynthesis and uptake to maintain cellular cholesterol homeostasis. Nevertheless, the prognostic value of <i>SREBF2</i> in CN-AML remains incompletely understood, necessitating further investigation to clarify its mechanistic role and clinical impact.</p> Methods <p>We explored the prognostic implications of <i>SREBF2</i> expression in two independent large-scale CN-AML patient cohorts. Using integrated multi-omics analysis of transcriptomic data, we characterized the molecular networks and pathways associated with <i>SREBF2</i>. Furthermore, we investigated the microRNA-target interaction network and epigenetic modifications of <i>SREBF2</i> to unravel its functional role in leukemogenesis.</p> Results <p>In an independent CN-AML cohort (<i>n</i> = 185), <i>SREBF2</i> overexpression was significantly associated with adverse overall survival (OS: <i>P</i> = 0.005) and event-free survival (EFS: <i>P</i> = 0.006). Stratified analysis confirmed prognostic significance across subgroups (NCCN Intermediate Risk: OS <i>P</i> = 0.003, EFS <i>P</i> = 0.019; non-M3: OS <i>P</i> = 0.005, EFS <i>P</i> = 0.021). Moreover, multivariable analysis confirmed <i>SREBF2</i> as an essential unfavorable element in CN-AML patients. Multi-omics analysis revealed <i>SREBF2</i>-associated molecular alterations, including leukemia-related gene co-expression, immune pathway dysregulation, microRNA/DNA methylation changes, and structural variants in the 1st exon/5’UTR region.</p> Conclusions <p>Our study identified <i>SREBF2</i> as a novel prognostic biomarker in CN-AML. Through gene enrichment and microRNA network analysis, <i>SREBF2</i> interactions with genomic/transcriptomic elements were found to drive CN-AML pathogenesis, providing clinical insights for treatment strategies.</p>

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Overexpression of Sterol Regulatory Element-binding Transcription Factor 2 is associated with an adverse prognosis in cytogenetically normal acute myeloid leukemia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月25日

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  • Ruoqi Shan,
  • Jiachi Wang,
  • Ping Chen,
  • Tingting Wu,
  • Fang Pang,
  • Ruoling Yang,
  • Yujun Wei,
  • Qiling Liu,
  • Yaowei Liu,
  • Ran Zhang,
  • Man Song,
  • Xia Li,
  • Lili Dong,
  • Cong Feng,
  • Sai Huang

摘要

Background

Cytogenetically normal acute myeloid leukemia (CN-AML), the most heterogeneous subgroup, requires molecular markers for effective management. Recent studies have highlighted abnormal lipid metabolism as a critical feature driving AML progression, and Sterol Regulatory Element-Binding Factor 2 (SREBF2) – a key regulator of cholesterol metabolism – orchestrates this process by controlling genes involved in sterol biosynthesis and uptake to maintain cellular cholesterol homeostasis. Nevertheless, the prognostic value of SREBF2 in CN-AML remains incompletely understood, necessitating further investigation to clarify its mechanistic role and clinical impact.

Methods

We explored the prognostic implications of SREBF2 expression in two independent large-scale CN-AML patient cohorts. Using integrated multi-omics analysis of transcriptomic data, we characterized the molecular networks and pathways associated with SREBF2. Furthermore, we investigated the microRNA-target interaction network and epigenetic modifications of SREBF2 to unravel its functional role in leukemogenesis.

Results

In an independent CN-AML cohort (n = 185), SREBF2 overexpression was significantly associated with adverse overall survival (OS: P = 0.005) and event-free survival (EFS: P = 0.006). Stratified analysis confirmed prognostic significance across subgroups (NCCN Intermediate Risk: OS P = 0.003, EFS P = 0.019; non-M3: OS P = 0.005, EFS P = 0.021). Moreover, multivariable analysis confirmed SREBF2 as an essential unfavorable element in CN-AML patients. Multi-omics analysis revealed SREBF2-associated molecular alterations, including leukemia-related gene co-expression, immune pathway dysregulation, microRNA/DNA methylation changes, and structural variants in the 1st exon/5’UTR region.

Conclusions

Our study identified SREBF2 as a novel prognostic biomarker in CN-AML. Through gene enrichment and microRNA network analysis, SREBF2 interactions with genomic/transcriptomic elements were found to drive CN-AML pathogenesis, providing clinical insights for treatment strategies.