Apoptosis in Lymphocytic Leukemias and Lymphomas

Abstract

Most current classifications of lymphoid neoplasms define the tumors based on the cell of origin, phenotype, genetic abnormalities, and clinical features. Here it is proposed that human lymphocytic tumors can be categorized based on the propensity and capacity of the tumor cells to undergo apoptosis. The first category is defined by malignant cells that are resistant to apoptosis due to expression of anti-apoptotic factors such as bcl-2 and cellular inhibitors of apoptosis (IAPs). These tumors would include CLL and follicular lymphomas, as well as some malignancies in which the tumor cells are infected by viruses that co-opt cell survival pathways, such as human T-cell leukemia/lymphoma virus (HTLV)-1. The second category, in which the malignant cells are apoptosis-prone, would include tumors arising in the context of impaired cytotoxic T-cell function. These neoplasms would include some human immunodeficiency virus (HIV)-related lymphomas such as Burkitt's lymphoma, and post-transplantation lymphomas. The third category would include neoplasms of intermediate sensitivity to apoptosis, some of which are associated with infection such as mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach. Although this classification is tentative, it should evolve in parallel with our understanding of pathogenic mechanisms in lymphoid neoplasia, and provides a novel framework with which to consider the appropriateness of specific therapeutic strategies. Distinctions among lymphocytic tumors in terms of the likelihood of response to therapies such as antisense to bcl-2 related proteins, inhibitors of NF-κB activity, and new approaches aimed at bolstering the host's immune response, would cross standard classifications based on the T or B-cell origin of the tumor cells.