Single-Antibody Evaluation of T-Cell Receptor β Constant Chain Monotypia by Flow Cytometry Facilitates the Diagnosis of T-Cell Large Granular Lymphocytic Leukemia

Am J Clin Pathol. 2021 Jun 17;156(1):139-148. doi: 10.1093/ajcp/aqaa214.


Objectives: The diagnosis of T-cell large granular lymphocytic leukemia (T-LGLL) is challenging because of overlapping immunophenotypic features with reactive T cells and limitations of T-cell clonality assays. We studied whether adding an antibody against T-cell receptor β constant region 1 (TRBC1) to a comprehensive flow cytometry panel could facilitate the diagnosis of T-LGLL.

Methods: We added TRBC1 antibody to the standard T-cell and natural killer (NK) cell panel to assess T-cell clonality in 56 T-LGLLs and 34 reactive lymphocytoses. In addition, 20 chronic lymphoproliferative disorder of NK cells (CLPD-NKs) and 10 reactive NK-cell lymphocytoses were analyzed.

Results: Clonal T cells were detected in all available T-LGLLs by monotypic TRBC1 expression and clonal/equivocal T-cell receptor gene rearrangement (TCGR) studies, compared with only 27% of T-LGLLs by killer-cell immunoglobulin-like receptor (KIR) restriction. Overall, 85% of T-LGLLs had a blood tumor burden greater than 500 cells/µL. Thirty-four reactive cases showed polytypic TRBC1 expression, except for 5 that revealed small T-cell clones of uncertain significance. All CLPD-NKs showed expected clonal KIR expression and negative TRBC1 expression.

Conclusions: Addition of TRBC1 antibody to the routine flow cytometry assay could replace the TCGR molecular study and KIR flow cytometric analysis to assess clonality, simplifying the diagnosis of T-LGLL.

Keywords: Flow cytometry; T-cell large granular lymphocytic leukemia; T-cell receptor β constant region 1.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Flow Cytometry / methods*
  • Humans
  • Leukemia, Large Granular Lymphocytic / diagnosis*
  • Leukemia, Large Granular Lymphocytic / immunology
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell, alpha-beta / analysis*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Single-Chain Antibodies*


  • Receptors, Antigen, T-Cell, alpha-beta
  • Single-Chain Antibodies