학술논문
Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry.
Document Type
Academic Journal
Author
Horna P; Division of Hematopathology, Mayo Clinic, Rochester, MN, USA. horna.pedro@mayo.edu.; Weybright MJ; Division of Hematopathology, Mayo Clinic, Rochester, MN, USA.; Ferrari M; Autolus Ltd, London, UK.; Jungherz D; Department of Internal Medicine, University of Cologne, Cologne, Germany.; Peng Y; Department of Internal Medicine, University of Cologne, Cologne, Germany.; Akbar Z; Autolus Ltd, London, UK.; Tudor Ilca F; Autolus Ltd, London, UK.; Otteson GE; Division of Hematopathology, Mayo Clinic, Rochester, MN, USA.; Seheult JN; Division of Hematopathology, Mayo Clinic, Rochester, MN, USA.; Ortmann J; Centre de Recherches Mathematiques, Universite du Quebec a Montreal, Montreal, Canada.; Shi M; Division of Hematopathology, Mayo Clinic, Rochester, MN, USA.; Maciocia PM; Cancer Institute, University College London, London, UK.; Herling M; Department of Internal Medicine, University of Cologne, Cologne, Germany.; Pule MA; Autolus Ltd, London, UK.; Cancer Institute, University College London, London, UK.; Olteanu H; Division of Hematopathology, Mayo Clinic, Rochester, MN, USA.
Source
Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101568469 Publication Model: Electronic Cited Medium: Internet ISSN: 2044-5385 (Electronic) Linking ISSN: 20445385 NLM ISO Abbreviation: Blood Cancer J Subsets: MEDLINE
Subject
Language
English
Abstract
The diagnosis of leukemic T-cell malignancies is often challenging, due to overlapping features with reactive T-cells and limitations of currently available T-cell clonality assays. Recently developed therapeutic antibodies specific for the mutually exclusive T-cell receptor constant β chain (TRBC)1 and TRBC2 isoforms provide a unique opportunity to assess for TRBC-restriction as a surrogate of clonality in the flow cytometric analysis of T-cell neoplasms. To demonstrate the diagnostic utility of this approach, we studied 164 clinical specimens with (60) or without (104) T-cell neoplasia, in addition to 39 blood samples from healthy donors. Dual TRBC1 and TRBC2 expression was studied within a comprehensive T-cell panel, in a fashion similar to the routine evaluation of kappa and lambda immunoglobulin light chains for the detection of clonal B-cells. Polytypic TRBC expression was demonstrated on total, CD4 + and CD8 + T-cells from all healthy donors; and by intracellular staining on benign T-cell precursors. All neoplastic T-cells were TRBC-restricted, except for 8 cases (13%) lacking TRBC expression. T-cell clones of uncertain significance were identified in 17 samples without T-cell malignancy (13%) and accounted for smaller subsets than neoplastic clones (median: 4.7 vs. 69% of lymphocytes, p < 0.0001). Single staining for TRBC1 produced spurious TRBC1-dim subsets in 24 clinical specimens (15%), all of which resolved with dual TRBC1/2 staining. Assessment of TRBC restriction by flow cytometry provides a rapid diagnostic method to detect clonal T-cells, and to accurately determine the targetable TRBC isoform expressed by T-cell malignancies.
(© 2024. The Author(s).)
(© 2024. The Author(s).)