Scholarlink

<p>The biological basis of the high clinical heterogeneity of T-LGL Leukemia (T-LGLL) is not completely understood and effective therapies for this disease are lacking. Through RNA-Sequencing of purified T-LGLs we reveal gene expression profiles and pathway dysregulations in the major patient subgroups, defined by CD8+ or CD4+ phenotype and <i>STAT3</i>/<i>STAT5B</i> mutational status. Overall, T-LGLL patients exhibited a marked transcriptome dysregulation compared to controls. This was more pronounced in the most symptomatic CD8 + <i>STAT3</i>-mutated patients, which emerged as a distinct biological entity, separated from the other disease subgroups. Particularly, CD8 + <i>STAT3</i>-mutated cases displayed extensive down-regulation of genes, ultimately resulting in the de-repression of proliferation and cell cycle pathways. Among genes up-regulated in CD8 + <i>STAT3</i>-mutated cases we found <i>VCAM1</i>, the transcriptional repressor EZH2 and the p53-regulator MDM2 proto-oncogene, as well as the leukemogenesis-associated <i>PVT1</i> up-regulation, representing the first report of a long-non-coding RNA alterations in leukemic T-LGLs. The impact of <i>STAT5B</i> mutations on T-LGLs transcriptome was more limited and the overexpression of the <i>PIM1</i> serine/threonine kinase proto-oncogene was identified as one of the most relevant features of <i>STAT5B</i>-mutated CD4 + T-LGLL. This study significantly advances our understanding of T-LGLL pathogenesis, uncovering new oncogenic mechanisms within the distinct molecular subtypes of the disease.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Transcriptomic landscape of CD8+ and CD4 + T-LGL leukemia revealed the distinct impact of STAT3 and STAT5B activating mutations

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月28日

查看全文
  • Giulia Calabretto,
  • Andrea Binatti,
  • Antonella Teramo,
  • Alessia Buratin,
  • Gregorio Barilà,
  • Vanessa Rebecca Gasparini,
  • Cristina Vicenzetto,
  • Enrico Gaffo,
  • Elisa Rampazzo,
  • Silvia Orsi,
  • Elena Buson,
  • Valentina Trimarco,
  • Barbara Mariotti,
  • Monica Facco,
  • Flavia Bazzoni,
  • Livio Trentin,
  • Gianpietro Semenzato,
  • Renato Zambello,
  • Stefania Bortoluzzi

摘要

The biological basis of the high clinical heterogeneity of T-LGL Leukemia (T-LGLL) is not completely understood and effective therapies for this disease are lacking. Through RNA-Sequencing of purified T-LGLs we reveal gene expression profiles and pathway dysregulations in the major patient subgroups, defined by CD8+ or CD4+ phenotype and STAT3/STAT5B mutational status. Overall, T-LGLL patients exhibited a marked transcriptome dysregulation compared to controls. This was more pronounced in the most symptomatic CD8 + STAT3-mutated patients, which emerged as a distinct biological entity, separated from the other disease subgroups. Particularly, CD8 + STAT3-mutated cases displayed extensive down-regulation of genes, ultimately resulting in the de-repression of proliferation and cell cycle pathways. Among genes up-regulated in CD8 + STAT3-mutated cases we found VCAM1, the transcriptional repressor EZH2 and the p53-regulator MDM2 proto-oncogene, as well as the leukemogenesis-associated PVT1 up-regulation, representing the first report of a long-non-coding RNA alterations in leukemic T-LGLs. The impact of STAT5B mutations on T-LGLs transcriptome was more limited and the overexpression of the PIM1 serine/threonine kinase proto-oncogene was identified as one of the most relevant features of STAT5B-mutated CD4 + T-LGLL. This study significantly advances our understanding of T-LGLL pathogenesis, uncovering new oncogenic mechanisms within the distinct molecular subtypes of the disease.