B cell
malignancies are classified according to the postulated differentiation stage of the originating cell. During differentiation, structural and molecular changes occur to support massive processing of
immunoglobulin in the endoplasmic reticulum (ER) of plasma cells at the final stage. When overloaded, the ER generates unfolded
proteins and
hydrogen peroxide (H2O2), which may cause cell death.
Peroxiredoxins (Prxs) I and IV belong to a family of
proteins able to catalyze
peroxide detoxification. Here, we investigated a potential association of these
enzymes with
immunoglobulin production in B cell
neoplasms. Our results demonstrated that the expression of Prx IV was induced as cells became competent to synthesize
immunoglobulin light chains, as observed by immunohistochemistry in tissue sections of B cell
neoplasms and also by qPCR and Western blotting analyses in malignant B cell lines. Prx I was frequently highly expressed, indicating additional regulatory processes besides ER activity. Results obtained exclusively with myeloma cells have shown that expression of Prxs I and IV, both at
mRNA and
protein levels, was associated with light chain secretion quantified by ELISA. We suggest that Prxs I and IV may provide survival advantages for terminally differentiated neoplastic B cells by the elimination of H2O2 and, in the case of Prx IV, by the conversion of this toxic in a functional agent driving oxidative protein folding in the ER. In this sense,
multiple myeloma and
lymphomas demonstrated to synthesize
immunoglobulin chains may benefit from strategic
therapies targeting the adaptive pathway to ER stress, including inhibition of Prxs I and IV activity.