SERIAL PHENOTYPIC, CYTOGENETIC AND MOLECULAR-GENETIC STUDIES IN RICHTERS-SYNDROME - DEMONSTRATION OF LYMPHOMA DEVELOPMENT FROM THE CHRONIC LYMPHOCYTIC-LEUKEMIA CELLS

In this report we describe a unique longitudinal study on the clinical , phenotypic, cytogenetic and molecular genetic features of malignant cells from diagnosis of chronic lymphocytic leukaemia (CLL) to the dev elopment of lymphoma and lymphomatous meningitis. CLL cells at diagnos is were CD5+, CD19+, surface IgG+, kappa+, were karyotypically abnorma l and showed clonal rearrangements in the immunoglobulin heavy (IgH) a nd kappa light chain genes. Phenotypically leukaemic cells and lymphom a cells at RS resembled CLL at diagnosis, but showed cytogenetic evolu tion. Geometrically leukaemic cells and lymphoma cells retained the in itial clonal rearrangements in IGH and kappa genes, but showed additio nal supervening clonal rearrangements in both of these genes as the di sease progressed to RS. Furthermore, the c-lambda DNA showed clonal re arrangements in the leukaemic cells and lymphoma cells at RS. This com plete phenotypic and genotypic analysis of tumour cells during the cou rse of the disease demonstrates the origin of lymphoma from CLL cells through progressive cytogenetic and molecular genetic changes in CLL c ells.