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Mature B-cell non-Hodgkin lymphoma (B-NHL), representing about 83% of all NHLs, is a heterogeneous group of malignancies involving uncontrolled clonal expansion of transformed B cells in the periphery. B-cell non-Hodgkin lymphoma (NHL) includes multiple clinicopathologic subtypes, most commonly diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).
The strongest and most consistent risk factors of B- NHL’s etiology are altered immunity conditions. Immunodeficiency, including both congenital immunodeficiency disorders and acquired conditions such as those observed in HIV-positive/AIDS patients and in transplant patients receiving immunosuppressive drugs, is a well-described and strong risk factor for NHL. Chronic antigenic stimulation by Epstein-Barr virus (EBV), hepatitis C virus or H. pylori, especially in a setting of impaired immune surveillance, is also associated with increased B-NHL risk. Moreover, autoimmune conditions, such as rheumatoid arthritis, Sjögren's disease, and systemic lupus erythematosus, are consistently associated with an increased risk of B-NHL, while atopic conditions, such as asthma, eczema and hay fever, may be associated with a decreased risk of NHL. A common characteristic of these conditions is the dysregulation of cytokines, which are known to play essential roles in immune cell development and immune functions. In addition, cytokines can directly stimulate B-cell proliferation, prevent B-cell apoptosis, and promote B-cell V(D)J recombination and isotype switching, which collectively enhance the likelihood of the chromosome translocations that are a hallmark of B-NHL. Translocations can activate proto-oncogenes such as c-myc and/or inactivate tumor suppressor genes which may ultimately lead to malignant transformation of B cells. Studied have also suggested that serum levels of certain cytokines, including sIL-2R, IL-5, IL- 13, TNF-α, and sTNF-R2, are associated with risk of B-NHL, and that multiple mechanisms, such as B-cell stimulation, pro-inflammatory activity, and impaired tumor surveillance, might be involved.
There has been tremendous insight gained in the last two decades from basic science research. New molecular targets in neoplastic cells are emerging and provide the rationale for clinical development of novel agents in non-Hodgkin lymphoma. These novel agents can be broadly categorized into two groups. The first is by immunotherapy which includes novel monoclonal antibodies and immunomodulating drugs, which make use of or optimizes immune system function. The other group of drugs targets small molecules that may play an important role in tumorigenesis. The mechanisms of anti-tumor activity include targeting apoptotic pathways, mammalian target of rapamycin (mTOR), inhibition of proteasomes, cyclin-dependent kinases and histone deacetylases. These novel agents and the various treatment approaches are currently being evaluated in non-Hodgkin lymphoma.
Creative Biogene, as a leading biotechnology company, is able to offer various B-NHL pathway related products including stable cell lines, viral particles and clones for your drug discovery projects.