Gene expression analysis in aggressive NHL.

The mRNA expression profile of a tumor reflects the unique genetic alterations present and is predictive of the clinical and biological characteristics of the tumor. Novel techniques have been developed to determine the global gene expression pattern of normal and neoplastic tissues. A cDNA microarray uniquely suitable for the analysis of B-cell non-Hodgkin's lymphomas (B-NHL) has been developed and preliminary analysis on diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and B-chronic lymphocytic leukemia (CLL) has been performed. These studies indicate that: 1) it is feasible to determine the gene expression profiles of archival lymphoma samples frozen and stored in a clinical setting, 2) the expression profile of these 3 types of lymphoproliferative disorders are distinctive, 3) DLBCL can be divided into at least 2 major subgroups according to their pattern of expression of B-cell associated genes and 4) the gene expression patterns in DLBCL appear to have prognostic significance. A larger study of DLBCL is currently underway to confirm and extend our findings. Gene expression profiles will be correlated with cytogenetic and clinical data to identify distinctive profiles that are of clinical and biological significance and to delineate key genetic lesions that determine these profiles. The new information will allow the design of a simpler and less expensive array for clinical use. The diagnostic array could provide rapid molecular characterization of every B-NHL at presentation for optimal treatment decisions and prognostication. It is anticipated that this project will advance our understanding of the molecular mechanisms in the neoplastic transformation of B-lymphoid cells and the new insights will help to identify promising molecular targets for therapeutic intervention.