Nature Immunology: Target on Specific Point of Protein Bcl6
Recently in Nature Immunology, researchers declaimed that we might have chance to shut down Bcl6 in DLBCL, while not affecting its vital function in T cells and macrophages that are needed to support a healthy immune system.
Diffuse large B-cell lymphoma (DLBCL), the seventhly commonly diagnosed cancer, is a frequently seen non-Hodgkin lymphoma. Many of current therapies can’t help DLBCL patients due to the drug resistance as well as high risk of relapse.
Bcl6, a master regulatory transcription factor, arises from the B-cells of the immune system. Transcription factors are responsible for either inhibiting or promoting the expression of genes; their actions regulate thousands of genes in different kinds of cells. Bcl6 can control the type of immune cell that develops in the bone marrow—playing many roles in the development of B cells, T cells, macrophages and other cells—including a primary and essential role in enabling B-cells to generate specific antibodies against pathogens. The protein has long been considered too complex to target with a drug since it is also crucial to the healthy functioning of many immune cells in the body, not just B cells gone bad. In the event of Bcl6 being inhibited, patients might suffer from systemic inflammation and atherosclerosis.
Thus researchers carried out this new study to help clarify the possible risks, as well as to understand how Bcl6 controls the various aspects of the immune system. In previous studies, scientists used RI-BPI, a peptide mimic, and the small molecule agent 79-6 to identify the target agent. Inspired by this, researchers started this study.
Not functioning as a single molecular machine, Bcl6 instead seems to have multiple tools to assist its roles. This multi-function paradigm could represent a general model for the functioning of other master regulatory transcription factors.
Based on this, scientists said we could specifically target on the single or multiple tools on Bcl6 accordingly without affecting the whole machine. They found a master regulator could separate its functions so precisely.
By this, researchers hope this will be a major benefit to the treatment of DLBCL and perhaps other disorders that are affected by Bcl6 and other master regulatory transcription factors.