Rearrangement and expression of T cell antigen receptor genes in B cell chronic lymphocytic leukemia

Abstract

Fifty-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.

Monoclonal B‐cell lymphocytosis in first‐degree relatives of patients with sporadic (non‐familial) chronic lymphocytic leukaemia

“…TRG clonal rearrangement was also found in two subjects from the MBL population. T‐cell receptor gene rearrangements other than those of the β chain genes (Chen et al , 1987; Dyer, 1989; Merup et al , 1994; Norton et al , 1988) are extremely rare in CLL (Kerlan‐Candon et al , 1998; Perl et al , 1990). As far as we know, the two cases described here are the first published cases of MBL harbouring clonal rearrangements of a T‐cell receptor gene, and probably they were detected because we have usually used a PCR strategy which includes consensus primers to search for TCR clones in all of our MBL cases.…”

Clonal T‐cell proliferation causing pure red cell aplasia in chronic B‐cell lymphocytic leukaemia: successful treatment with cyclosporine following in vitro abrogation of erythroid colony‐suppressing activity

“…In this study we first addressed the occurrence of clonal T‐cell populations in B‐cell CLL by T‐cell receptor gene analysis, because clonal crosslineage rearrangements of the TCR‐β chains can occur in B‐cell leukaemias ( Norton et al , 1988 ). We detected the clonally rearranged TCR‐β gene in the DNA from the T‐cell‐enriched fraction obtained from the patient on admission.…”

Gene probe analysis demonstrates independent clonal evolution of co‐existent chronic myeloid and chronic lymphocytic leukaemia

“…High molecular weight DNA was prepared from peripheral blood and bone marrow collected at the time of the second bone marrow examination (4 wk after commencing treatment for CML) using standard pro- (11). Hybridisation studies were performed as described previously (12) using two probes: I) a 1.2 kb Hind III -Bg] 11 fragment of the breakpoint cluster region (bcr) of the Ph gene (Oncogene Science Inc .• Mincola, N. Y.)…”