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

ABSTRACT: 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 path

SUBMITTER: Calabretto G 

PROVIDER: S-EPMC12463674 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature