Molecular characterization and functional studies of human B cell lymphoma

Malignant lymphomas represent a heterogeneous group of diseases with variable clinical course. Our group aims at identifying genes/signalling pathways with prognostic, diagnostic or therapeutic potential in B cell lymphomas. We are one of 7 groups that co nstitute the newly established Centre for Cancer Biomedicine at the Institute and we are part of the lymphoma milieu at our hospital. Studies of genetic aberrations and changes in gene expression by use of microarray analyses represents a central part of our research activity. We are involved in a broad international collaboration led from NCI regarding a broad molecular characterization of Non Hodgkins lymphoma by use of gene expression profiling. Three distinct subgroups of diffuse large B cell lymphoma have been identified and these have different prognosis and pathogenesis. For several of the major lymphoma subtypes, we have found that expression of different sets of genes are strongly correlated to prognosis. We have now also entered a prospecive di agnostic study to test the applicability of a specially designed chip in the routine diagnostics of lymphoma (1/8 centres world-wide). We also use high throughput analyses to study genetic changes in relation to progression of follicular lymphoma. In addi tion, we collaborate with the lymphoma milieu regarding biological and molecular studies in relation to clinical studies. Studies to explore the role of abberant signalling pathways represent another main research activity. We have established good in vit ro systems to study fnctional responses in normal and neoplastic B cells. We now focus on the role of members of the TGF-beta/BMP (bone morphogenic protein) family and downstream target genes (including Id-proteins) and the PI3-kinase/Akt pathway. We have also identified several genes with interesting expression profiles in B lymphoid cells, and will study the functional role of these genes with the goal to develop novel diagnostic and therapeutic potential.