Ten patients with large granular lymphocyte (LGL) leukemia were studied for rearrangement and expression of T cell receptor (TCR) genes. Eight patients with CD3+ LGL proliferation had unique TCR beta-gene rearrangements, supporting a clonal process. Each of five patients studied with CD3+ disease had evidence for expression of full-length TCR alpha-, beta-, and gamma-gene transcripts. In contrast, patients with CD3- LGL proliferation had no evidence for rearrangement or expression of TCR genes. These studies suggest that leukemic LGL arise from two different cell origins. Leukemic LGL may be a useful model for studying natural killer (NK) cell (CD3- LGL) and non-MHC-restricted cytotoxic T lymphocyte (CD3+ LGL) activation and differentiation.

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