Inborn errors of immunity underlie clonal T cell expansions in large granular lymphocyte leukemia.

ABSTRACT: BACKGROUNDT cell large granular lymphocyte leukemia (T-LGLL) is a lymphoproliferative disorder of cytotoxic T lymphocytes (CTLs), often with gain-of-function STAT3 mutations. T-LGLL represents a unique model for the study of persistent CTL expansions. Albeit autoimmunity is implied, various paradoxical observations led us to investigate whether immunodeficiency traits underpin T-LGLL.METHODSThis is a comprehensive immunogenomic study of 92 consecutive patients from a large T-LGLL cohort with full laboratory-clinical characterization (n = 271). Whole-exome profiling of variants associated with inborn errors of immunity (IEI) and somatic mutations in T cell lymphoid drivers was analyzed. Single-cell RNA-Seq and TCR-Seq in T-LGLL samples and RNA-Seq in T cell cancer cell lines were utilized t

SUBMITTER: Bravo-Perez C 

PROVIDER: S-EPMC12043085 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature