The interaction between Bcl-6 and STAT6 pathway in non -Hodgkin lymphoma
Abstract
Non-Hodgkin lymphoma is a heterogeneous group of malignancies that has continued to increase in both frequency and death rate since the 1950's. The Bcl-6 proto-oncogene was first identified by its involvement in chromosomal translocations in non-Hodgkin lymphoma, particularly diffuse large cell lymphoma and follicular lymphoma. One of the most well described functions of Bcl-6 is as a competitive inhibitor of IL-4 induced STAT6-mediated gene expression. In this study, we examined the interaction of Bcl-6 and the STAT6 pathway in non-Hodgkin lymphoma and normal B cells, and how this interaction was changed in response to stimulation with various B cell activating agents. Our results showed that Bcl-6 could be up-regulated in normal B cells and follicular lymphoma patient cells in response to activation with various combinations of CD40L, anti-IgM, PMA and ionomycin. Diffuse large cell lymphoma cell lines that did not express Bcl-6 could not up-regulate it in response to these stimuli, while diffuse large cell lymphoma cell lines that were Bcl-6 positive down-regulated its expression following stimulation with these agents. In addition, normal B cells and follicular lymphoma grade II patient cells could up-regulate P-STAT6 upon stimulation with these agents, while the diffuse large cell lymphoma cell lines could not. The STAT6 pathway was present and functional in the diffuse large cell lymphoma cell lines as shown by the presence of P-STAT6 following stimulation with exogenous IL-4. Two diffuse large cell lymphoma cell lines, one Bcl-6 protein negative and one Bcl-6 protein positive, could up-regulate Bcl-6 protein expression in response to prolonged IL-4 stimulation. This up-regulation corresponded to increases in P-STAT6 expression and cellular proliferation. Therefore, we concluded that Bcl-6 and STAT6 do not act as competitive inhibitors in diffuse large cell lymphoma cell lines. This lack of competitive inhibition would allow the B cell to proliferate without normal cell cycle controls, and could be one of the transforming events leading from normal B cells and indolent lymphomas to aggressive B cell lymphomas.
Subject Area
Immunology|Oncology
Recommended Citation
Bunce, Kimberly Diane, "The interaction between Bcl-6 and STAT6 pathway in non -Hodgkin lymphoma" (2006). Texas Medical Center Dissertations (via ProQuest). AAI3218711.
https://digitalcommons.library.tmc.edu/dissertations/AAI3218711