Studies of growth control and gene expression in normal and neoplastic B-lymphoid cells

Malignant lymphomas represent a heterogeneous group of diseases with variable clinical course. The complex biology and the variety of genetic and epigenetic factors involved in the pathogenesis make lymphomas a challenging disease for translational resear ch. There a clear need for the development of novel diagnostic and therapeutic tools. The current project will be part of a broad collaborative effort at our institution. We will use microarray technology to study genetic changes and gene expression in ma lignant lymphomas to obtain further insight into the molecular mechanisms involved in lymphomagenesis and to identify possible novel molecular targets for diagnostic and therapeutic use. We have important international collaboration representing major con tributors in the field. In particular, we are involved in a collaborative effort for molecular profiling of B cell lymphomas coordinated by NCI (The lymphoma and leukaemia molecular profiling project, LLMPP). We will also use in-house microarrays to study genomic alterations in relapsed follicular lymphoma and tissue arrays to study transformation of follicular lymphomas. Functional studies of normal and neoplastic B cells will also be an important part of the project. We have wide experience in isolation , characterisation and in vitro cultures of various B cell populations. We will focus on the role of normal and malignant B cells of bone morphogenic protetins (BMPs), and signal transduction cascades including the P13K/Akt pathway.