Mechanisms that contribute to the development of lymphoid malignancies: roles for genetic alterations and cytokine production

Abstract

Recent studies have defined genetic alterations commonly associated with transformed lymphocytes. This review suggests roles for these alterations in the development of lymphoid neoplasms. Damage to the genes encoding proteins that function in intracellular signaling, transcription, or regulation of the cell cycle has been identified and linked at varying degrees to the progression of certain lymphoid malignancies. An understanding of the mechanistic consequences following such genetic alterations is essential to an understanding of the development of these lymphoid neoplasms. In contrast, it is also becoming clear that the 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 of cytokines which accompanies many lymphoproliferative diseases. The dysregulated expression of cytokines during malignancy can result in the augmentation of growth of transformed lymphocytes, as well as an alteration of the anti-tumor immune response. The latter mechanism is especially important because evasion of the impending immune response is a prerequisite for the progression of lymphoproliferative diseases. Taken together, this review supports the notion that the development of lymphoid malignancies is multifactorial, involving genetic alterations as well as dysregulated cytokine expression.