Rearrangement and expression of T cell antigen receptor genes in B cell chronic lymphocytic leukemia
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AbstractFifty-nine patients with B cell chronic lymphocytic leukemia (B-CLL) were screened for clonal rearrangement of T cell receptor (TCR) beta and gamma chain genes. Four were found with rearranged TCR beta genes, but none had detectable rearrangement of TCR gamma genes. One typical patient with B-CLL had a TCR beta gene structure consistent with a variable-diversity-joining rearrangement into the C beta 2 gene on one allele. An apparently identical rearrangement pattern was seen in a second patient, which suggested that there may be a restriction on the repertoire of possible TCR beta gene recombinations in mature B cells. Two further patients had a simple deletion of sequences, consistent with a diversity-joining rearrangement into C beta 2 on one allele. All four patients had rearrangements of immunoglobulin heavy- and light- chain genes typical of mature B cell malignancies. However, on review of clinical, morphological, and immunophenotype data, two had features consistent with B cell prolymphocytic leukemia or B lymphoma, and a third had progressed to a prolymphocytic transformation. Low-level expression of a predominantly 1.0- to 1.2-kilobase germ line TCR beta gene transcript was detected in several B-CLLs and at a comparable level in the four with rearranged TCR beta genes. This, together with the low frequency of TCR gene rearrangement, suggests that most B-CLL cases arise at a developmental stage when factors required for TCR gene activity are not operative.
