The Gene Expression Profiles of Indolent Lymphomas

Abstract

Follicular lymphoma is an indolent form of non-Hodgkin's lymphoma. Due to its slow growing nature, it is difficult to treat because of the inability to target slow dividing cells. Calcineurin, (CN) is a protein phosphatase (PP2B) has been shown to be involved in the apoptosis of lymphocytes in vitro cell culture system. CN is composed of a regulatory subunit CN B and a catalytic subunit CN A. Three isoforms of CN A (α, β, and γ) are expressed in various tissues. CN is the target for immunosuppressive drugs cyclosporine A and tacrolimus (FK506) because of CN's critical role in lymphocyte responses. In CNAβ knock-out mice, it was found that mice lacking this gene are prone to develop splenomegaly and lymphoma. This is because CNAβ is acting as a tumor suppressor, thus mice lacking this gene develop cancer. RNA was prepared from spleens of Cnab^(-/-) and control mice and gene expressions levels were measured by affymetrix microarray chips. Future studies will evaluate the gene expression profiles by quantitative real time PCR and immunohistochemistry to validate the expression of the candidates in lymphomagenesis. This mouse model will be the first mouse model for indolent lymphomas and has a potential for development of therapeutic interventions not only for lymphomas but also for other cancers and transplant tolerance.