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ß+ Large Granular Lymphocytes
From the Serviço de Hematologia Clínica,*
Unidade de Citometria, Hospital Geral de Santo António, Porto,
Portugal; and the Servicios de
Citometría
y
Hematología,
Hospital Universitario
de Salamanca and Centro de Investigación del Cáncer,
Universidad de Salamanca, Salamanca, Spain.
At present, a major challenge in the initial diagnosis of
leukemia of large granular lymphocytes (LGLs) is to establish the
clonal nature of the expanded population. In the present study we have
analyzed by flow cytometry immunophenotyping the TCR-Vß repertoire of
98 consecutive cases of persistent expansions of CD4+ or
CD8+bright CD3+/TCR-
ß+ LGLs
and compared the results with those obtained in molecular studies of
TCR-ß gene rearrangements. Fifty-eight cases were considered to be
monoclonal in molecular studies whereas in the remaining 40 cases there
was no evidence for monoclonality (11 cases were considered oligoclonal
and 29 polyclonal). The TCR-Vß repertoire was biased to the
preferential use of one or more TCR-Vß families in 96% of
cases, a total of 124 TCR-Vß expansions being diagnosed: one
TCR-Vß expansion in 71 cases and two or more TCR-Vß expansions in
23 cases. The highest TCR-Vß expansion observed in each case was
higher among monoclonal (74 ± 19%) as compared to nonmonoclonal
cases (24 ± 14%) (P = 0.001), as did
the fraction of LGLs that exhibited a TCR-Vß-restricted pattern
(86 ± 16% and 42 ± 23%, respectively;
P = 0.0001); by contrast, the proportion of
cases displaying more than one TCR-Vß expansion was higher in the
latter group: 7% versus 48%, respectively
(P = 0.001). Results obtained in oligoclonal cases
were intermediate between those obtained in polyclonal and monoclonal
cases and similar results were observed for CD4+ as
for CD8+bright T-cell expansions. TCR-Vß
familiesexpressed in CD8+bright T-cell-LGL
proliferations showed a pattern of distribution that mimics the
frequency at which the individual TCR-Vß families are represented in
normal peripheral blood T cells. Assuming that a given proliferation of
LGLs is monoclonal whenever there is an expansion of a given TCR-Vß
family of at least 40% of the total CD4+ or
CD8+bright T-cell compartment, we were able to
predict clonality with a sensitivity of 93% and a specificity of 80%.
By increasing the cut-off value to 60%, sensitivity and
specificity were of 81% and 100%. In summary, our results
suggest that flow cytometry immunophenotypic analysis of the TCR-Vß
repertoire is a powerful screening tool for the assessment of T-cell
clonality in persistent expansions of TCR-ß+
LGLs.
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