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This work was supported by the CB16/12/00400 (CIBERONC) and PI20-01346 grants from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion (Madrid, Spain) and FONDOS FEDER; the 0639-IDIAL-NET-3-3 grant (INTERREG POCTEP Spain-Portugal) from Fondo Europeo de Desarrollo Regional, and by the EuroFlow Foundation (Leiden, The Netherlands). N.M.-G. was supported by a pre-doctoral grant (Ref. IBPredoc17/00012) from IBSAL (Salamanca, Spain). M.L., N.V., J.J.M.v.D., A.O. and J.A. are members of the EuroFlow Consortium, www.euroflow.org (accessed on 16 December 2021).

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High-Sensitive TRBC1-Based Flow Cytometric Assessment of T-Cell Clonality in Tαβ-Large Granular Lymphocytic Leukemia

Publicated to:Cancers. 14 (2): 408- - 2022-01-01 14(2), DOI: 10.3390/cancers14020408

Authors: Munoz-Garcia, N; Moran-Plata, FJ; Barrena, S; Mateos, S; Caldas, C; van Dongen, JJM; Orfao, A; Almeida, J; Villamor, N; Lima, M

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Abstract

Flow cytometric (FCM) analysis of the constant region 1 of the T-cell receptor ? chain (TRBC1) expression for assessing T??-cell clonality has been recently validated. However, its utility for the diagnosis of clonality of T-large granular lymphocytic leukemia (T-LGLL) needs to be confirmed, since more mature T?? cells (i.e., T-LGL normal-counterpart) show broader TRBC1+/TRBC1- ratios vs. total T?? cells. We compared the distribution and absolute counts of TRBC1+ and TRBC1- T??-LGL in blood containing polyclonal (n = 25) vs. clonal (n = 29) LGL. Overall, polyclonal TRBC1+ or TRBC1- T??-LGL ranged between 0.36 and 571 cells/?L (3.2-91% TRBC1+ cells), whereas the clonal LGL cases showed between 51 and 11,678 cells/?L (<0.9% or >96% TRBC1+ cells). Among the distinct TCRV? families, the CD28- effector-memory and terminal-effector polyclonal T?? cells ranged between 0 and 25 TRBC1+ or TRBC1- cells/?L and between 0 and 100% TRBC1+ cells, while clonal LGL ranged between 32 and 5515 TRBC1+ or TRBC1- cells/?L, representing <1.6% or >98% TRBC1+ cells. Our data support the utility of the TRBC1-FCM assay for detecting T-cell clonality in expansions of T??-LGL suspected of T-LGLL based on altered percentages of TRBC1+ T?? cells. However, in the absence of lymphocytosis or in the case of T??CD4-LGL expansion, the detection of increased absolute cell counts by the TRBC1-FCM assay for more accurately defined subpopulations of T??-LGL-expressing individual TCRV? families, allows the detection of T-cell clonality, even in the absence of phenotypic aberrations.

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