Abstract
B-chronic lymphocytic leukemia (B-CLL), the most common human leukemia, is characterized by predominantly non-dividing malignant mature CD5+ B lymphocytes with an apoptosis defect. Various microenvironmental stimuli confer a growth advantage on these leukemic cells and extend their survival in vivo. Nevertheless, when cultured in vitro, CLL B-cells rapidly die from apoptosis. Certain cytokines may extend the survival capacity of CLL B-cells in vitro and individual anti-apoptotic effects of several cytokines have been reported. The potential cumulative effect of such cytokines has not been studied. We therefore investigated the effects on CLL B-cells survival in vitro of humoral factors, polyclonal lymphocyte activators and a combination of cytokines known for their anti-apoptotic effects. Purified CLL B-cells were cultured in the presence or absence of various soluble molecules and the leukemic cell response was assessed in terms of viability. Apoptotic cell death was detected by flow cytometry using annexinV and 7-amino-actinomycin. The survival of CLL B-cells in vitro was highly variable. When tested separately, cytokines (IL-2, -6, -10, -12, -15, -21, BAFF and APRIL) improved CLL B cell survival moderately; in combination, they significantly enhanced survival of these cells, even up to 7 days of culture. We also report that humoral factors from autologous serum are important for survival of these malignant cells. Our findings support the concept that the CLL microenvironment is critical and suggest that soluble factors may contribute directly to the prolonged survival of CLL B-cells. Therefore, the combination of cytokines we describe as providing strong resistance to apoptosis in vitro might be used to improve the treatment of CLL.
Highlights
B-chronic lymphocytic leukemia (B-CLL), the most common human leukemia, involves the accumulation of predominantly quiescent CD5+ B cells driven by the proliferation of a subpopulation [1]
Effect of cytokines on survival of CLL B-cells in vitro The effects of nine cytokines
Programmed cell death or apoptosis is a common form of cell elimination that can be activated in different cell types in response to a number of physiologically relevant stimuli
Summary
B-chronic lymphocytic leukemia (B-CLL), the most common human leukemia, involves the accumulation of predominantly quiescent CD5+ B cells driven by the proliferation of a subpopulation [1] In addition to this atypical proliferative profile, the B-CLL cells exhibit a strong dependence on cellular and cytokine components of their microenvironment, making their manipulation ex vivo complex and resulting in biased findings [2]. The B-CLL cells isolated from these tissues exhibit heterogeneity in their transcriptional, phenotypic, proliferative and apoptotic profiles dictated by the local microenvironments [3,4,5,6] Studies of these tissues and the extrapolation from our knowledge of normal B cell biology [7] suggest that the lymph node is the seat of B-CLL pathogenesis. For reasons of inaccessibility and ethics, almost all relevant scientific studies have addressed peripheral blood leukemic cells, only partially reflecting
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
