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 f or individual T lymphocytes by developmentally regulated gene rearrang ements and shaped by predominantly intrathymic selection procedures. T CR gene probes in Southern blot experiments and TCR primers for the po lymerase chain reaction (PCR) help to distinguish polyclonal from abno rmal clonal T cell proliferations and to monitor clonal disease after treatment. Rearrangement studies can identify the lineage and developm ental stage of a lymphocyte clone. Cross-lineage rearrangements, false positive or negative results are rarely misleading when morphology an d immunophenotypical findings are considered. Rearrangement studies, h owever, have not contributed significantly to the comprehension of lym phomagenesis Analyses of characteristic chromosomal translocations In T cell leukaemias and lymphomas may provide further insight into the m echanisms of malignant transformation. Transcription factors are often involved and sometimes abnormally transcribed, which may alter the ph ysiological intracellular signalling in T cells. Interphase cytogeneti c analysis by chromosomal fluorescence in situ hybridization (FISH) ha s become a new tool in the search for transformed T cells carrying spe cific translocations. Archival biopsy material is now accessible for P CR rearrangement studies and FISH cytogenetics. This adds another dime nsion to the diagnosis, disease monitoring and biological understandin g of malignant T cell lymphomas and leukaemias.