IP: Dra. Julia Almeida Parra

Resumen del proyecto: Chronic lymphocytic leukaemia (CLL) is the most frequent haematological malignancy in the western world. Currently it is accepted that CLL could be preceded by a clinically silent monoclonal B-cell lymphocytosis (MBL), small mature B-cell clones with a CLL-like phenotype being detected in up to 12% of otherwise healthy adults. This project aims at gaining insight into the genetic characteristics and the intracellular signalling pathways involved in the ontogenesis of MBL and progression of MBL clonal B-cells to CLL. Three study groups will be included: adult healthy donors (non-MBL) representative of the population of Salamanca (n=300), MBL without (n=90) and with lymphocytosis (n=60) and CLL (n=100). In each sample of purified clonal B-cells we will search for the presence of genetic abnormalities, sequence the IGHV/IGKV/IGLV genes and perform a massive SNP genotyping, aimed at identifying differential patterns of genetic alteration/predisposition among the three groups of individuals. In a subgroup of 60 MBL and 30 CLL the genetic study will be completed with the analysis of the length of telomeres and a phenotypic/proteomic characterization of the signalling pathways associated with BCR/CD79, cell proliferation, and senescence. In a subset of 25 biclonal cases (MBL and CLL) we will screen for antigens which bind to the BCR (NAPPA technique), aiming at identifying antigen specificities shared by different clones/cases. Finally, we will determine the relationship existing between the different altered patterns detected (at both the genetic and phenotypic/proteomic levels) and the status of the B-cell expansion, the behaviour of the B-cell clone and patient outcome.

Entidad financiadora: Instituto de Salud Carlos III