Study of the unfolded protein response in B-cell lymphoid malignancies and ynergism of proteasome inhibitores and pharmacological ER-stress inducers

Proteasome inhibition is a new treatment modality for multiple myeloma and non-Hodgkin lymphoma. It is possible that manipulation of the unfolded protein response (UPR) can enhance and improve their treatment possibilities. Therefore the pro- and anti-apoptotic arms of the UPR will be mapped in lymphoma cell lines corresponding with the different stages of differentiation of the lymphocyte to plasma cell. Second the synergism of proteasome inhibitors and pharmacological UPR-inducers will be tested, with most attention for the anti-apoptotic role of XBP-1 splicing and ATF6 cleavage.