Poster abstracts
Poster number 57 submitted by Mariam Salem
Understanding the role of Aiolos in the early lymphopoiesis of Bcl2-hyper expressing B cells
Mariam A Salem (Molecular, Cellular and Developmental Biology Graduate Program, Columbus, OH, 43210, USA), Kruthika Sharma (Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH, 43210, USA. ), Melissa R Leonard (Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH, 43210, USA. ), Srijana Pokhrel (Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH, 43210, USA. ), Kenneth J Oestreich (Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH, 43210, USA. ), Patrick L Collins (Department of Microbial Infection and Immunity, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, OH, 43210, USA. )
Abstract:
Apoptosis in lymphocytes prevents autoimmunity, leukemogenesis, and lymphomagenesis. BCL-2 is a guardian, preventing cell death, and its over-expression allows B cell survival in the absence of cytokines and is associated with multiple hematological malignancies. The t(14;18) rearrangement juxtaposes the B cell receptor- heavy chain locus to the anti-apoptotic factor Bcl2. That puts Bcl2 under the power of the enhancer mu, resulting in maintained, extremely high levels of Bcl2 expression. Continued rounds of germinal center activity, allow uncontrolled mutation and evolution of follicular lymphoma. Recent studies have shown that the drug lenalidomide, which targets the transcription factors Ikaros and Aiolos for degradation, is effective in the treatment of follicular lymphoma. Of the two, Aiolos has specialized roles in governing marginal zone B cell versus follicular cell fate, and the maintenance of long-lived plasma cells. Ikaros is essential for B cell development and its targeting often leads to severe effects in patients. Hence, we aimed to investigate the impact of selectively targeting Aiolos, as this has not been previously explored, to determine whether it could be effective with fewer adverse consequences. We sought to understand if Aiolos has a role in maintaining the survival and differentiation of Bcl2-over expressing B cells. We knocked out Aiolos in a follicular lymphoma mouse model, overexpressing Bcl2, and show that B cells have increased rate of apoptosis and are not able to leave the bone marrow and reach peripheral organs effectively. This study is the first to demonstrate the potential of evaluating Aiolos as a therapeutic target.
Keywords: Immunology, Cancer, B cells