Gene rearrangements and chromosomal translocations in T cell lymphoma--diagnostic applications and their limits

The diversity of the T cell receptor (TCR) repertoire is established for individual T lymphocytes by developmentally regulated gene rearrangements and shaped by predominantly intrathymic selection procedures. TCR gene probes in Southern blot experiments and TCR primers for the polymerase chain reaction (PCR) help to distinguish polyclonal from abnormal clonal T cell proliferations and to monitor clonal disease after treatment. Rearrangement studies can identify the lineage and developmental stage of a lymphocyte clone. Cross-lineage rearrangements, false positive or negative results are rarely misleading when morphology and immunophenotypical findings are considered. Rearrangement studies, however, have not contributed significantly to the comprehension of lymphomagenesis. Analyses of characteristic chromosomal translocations in T cell leukaemias and lymphomas may provide further insight into the mechanisms of malignant transformation. Transcription factors are often involved and sometimes abnormally transcribed, which may alter the physiological intracellular signalling in T cells. Interphase cytogenetic analysis by chromosomal fluorescence in situ hybridization (FISH) has become a new tool in the search for transformed T cells carrying specific translocations. Archival biopsy material is now accessible for PCR rearrangement studies and FISH cytogenetics. This adds another dimension to the diagnosis, disease monitoring and biological understanding of malignant T cell lymphomas and leukaemias.