KLRG1 re-defines a leukemic clone of CD8 effector T cells sensitive to PI3K inhibitor in T cell large granular lymphocytic leukemia.

ABSTRACT: T cell large granular lymphocytic leukemia (T-LGLL) is a clonal lymphoproliferative disorder, originated from mature effector memory CD8⁺ T cells. It is a challenge to define the leukemic T cell clones due to the lack of definite markers. Here, we decipher the heterogeneity of CD8⁺ T cells using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and T cell receptor (TCR) profiling in T-LGLL patients. A CD8⁺ terminal effector subset is identified, marked by reduced KLRG1 expression. Remarkably, high fidelity of leukemic clonality was specially limited in KLRG1^- large granular lymphocytes (LGLs), not seen in KLRG1⁺ LGLs in T-LGLL patients or in KLRG1^- LGLs in healthy controls. KLRG1^- leukemic

SUBMITTER: Zhang L 

PROVIDER: S-EPMC12047471 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature