In response to the treatment of TNF-α, TNF-α expression and TNFR1 expression on the surface of AM as well as LC3I expression were increased, autophagy was decreased, and LC3, LC3II, Beclin1 and B-cell lymphoma 2 expressions decreased, whereas FAS expression and activity and expression of caspase-3 and caspase-8 increased, and apoptotic index increased.
Levels of several proapoptotic proteins, such as FAS, FAS-ligand and BAX (B-cell lymphoma 2 associated X) were increased following amentoflavone treatment.
To further investigate this, we have performed extensive CD95 transcript sequencing and functional analysis in B-NHL with demonstrated resistance to CD95-induced apoptosis (B-NHLr).
The FAS antigen (CD95/APO-1) is suggested to be a tumor suppressor gene since mice and patients with congenital FAS mutations are prone to B cell lymphomas and somatic FAS mutations are described in hematological and solid tumors.
This review will focus on the potential role of the CD95-CD95 ligand system in the pathogenesis of hematological malignancies, with particular emphasis on recent work from our laboratory examining the expression of CD95 in B cell lymphomas.
We propose that CD95 mutations in B-cell lymphomas originate from the GC reaction and are introduced most probably as targeting errors of the somatic hypermutation machinery, which bears--besides its physiological role--an inherent risk of malignant transformation and the persistence of autoreactive B-cell specificities.
Recent studies identified deleterious mutations of the CD95 gene not only in a variety of B cell lymphomas but also in a number of solid tumor entities.
Since marginal zone B cell lymphomas usually arise in a background of chronic inflammation, often of autoimmune origin, we searched for CD95 gene mutations in an unselected series of marginal zone B cell lymphomas.