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Decreased T-Cell Receptor Excision Circles in Cutaneous T-Cell Lymphoma

Authors' Affiliations: ¹ Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, and ² Biostatistics Core Facility, Dana-Farber Harvard Cancer Center, Department of Biostatistics, Dana-Farber Cancer Institute, Boston, Massachusetts

Requests for reprints: Thomas S. Kupper, Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Boston, MA, 02115. Phone: 617-525-5550; Fax: 617-525-5571; E-mail: tskupper{at}rics.bwh.harvard.edu.

Purpose: The T cell repertoire in patients with advanced cutaneous T cell lymphoma (CTCL) is significantly contracted despite the presence of relatively normal absolute numbers of T cells. We propose that many normal T cells were being lost in patients with CTCL, with the remaining normal T cells expanding clonally to fill the T cell compartment. T-cell receptor excision circles (TREC) form as a result of the initial gene rearrangement in naïve T cells. Although they are stable, they do not replicate and are subsequently diluted with the expansion of a population of T cells. Their concentration is therefore a measure of unexpanded naïve T cells relative to T cells that have undergone expansion.

Experimental Design: We analyzed TRECs from unfractionated peripheral blood T cells from 108 CTCL patients by quantitative PCR. In patients with obvious peripheral blood involvement, we also analyzed TRECs from clonal and nonclonal T cells.

Results: We found a decrease in the number of TRECs in peripheral blood of patients with CTCL at all stages of disease, and this decrease was proportional to the loss of complexity of the T cell repertoire as measured by complementarity-determining region 3 spectratyping. In patients with leukemic CTCL and a numerically expanded clone, we also found a significantly lower-than-expected number of TRECs in the nonclonal normal T cells.

Conclusions: We hypothesize that the nonmalignant T cells have proliferated to fill the empty T cell repertoire space left by the loss of other T cells, leading to diminished TRECs and loss of T-cell receptor diversity.

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