Disruption of the IFN-gamma cytokine network in chronic lymphocytic leukemia contributes to resistance of leukemic B cells to apoptosis

Recent evidence indicates that the slowly expanding population of CD5 + B c ells that characterizes chronic lymphocytic leukemia (CLL) results primaril y from defects in responses to cytokines that regulate apoptosis (e.g. Il-4 , TGF-beta, IFN-alpha, IFN-gamma). We have now demonstrated not only that t he enhanced anti-apoptotic effect of IFN-gamma on these neoplastic B cells is apparently mediated through increased levels of IFN-gamma receptors but also that there are increased numbers of IFN-gamma-expressing CD4 and CDS T cells in these patients. This is the strongest evidence to date that multi ple alterations in the IFN-gamma cytokine network contribute to the pathoge nesis of CLL. (C) 2000 Elsevier Science Ltd. All rights reserved.