MECHANISMS THAT CONTRIBUTE TO THE DEVELOPMENT OF LYMPHOID MALIGNANCIES - ROLES FOR GENETIC ALTERATIONS AND CYTOKINE PRODUCTION

Recent studies have defined genetic alterations commonly associated wi th transformed lymphocytes. This review suggests roles for these alter ations in the development of lymphoid neoplasms. Damage to the genes e ncoding proteins that function in intracellular signaling, transcripti on, or regulation of the cell cycle has been identified and linked at varying degrees to the progression of certain lymphoid malignancies. A n understanding of the mechanistic consequences following such genetic alterations is essential to an understanding of the development of th ese lymphoid neoplasms. In contrast, it is also becoming clear that th e dysregulated expression of proteins that are not genetically altered can also contribute to the progression of lymphoid malignancies. One such example is the excessive expression of ''normal'' lymphokines or cytokines which accompanies many lymphoproliferative diseases. The dys regulated expression of cytokines during malignancy can result in the augmentation of growth of transformed lymphocytes, as well as an alter ation of the anti-tumor immune response. The latter mechanism is espec ially important because evasion of the impending immune response is a prerequisite for the progression of lymphoproliferative diseases. Take n together, this review supports the notion that the development of ly mphoid malignancies is multifactorial, involving genetic alterations a s well as dysregulated cytokine expression.