These data indicate that targeting XBP-1 has potential as a treatment strategy, not only for multiple myeloma, but also for mature B cell leukemia and lymphoma.
Expression of XBP-1 and other regulators of the unfolded protein response were measured in myeloma and other cancer cell lines and two cohorts of patients with refractory myeloma and correlated with sensitivity/response to bortezomib.
The similarities of this model with the human disease, coupled with documented frequent XBP-1s overexpression in human MM, serve to implicate XBP-1s dysregulation in MM pathogenesis.
Analysis of XBP-1, a transcriptional inducer of chaperones, in freshly isolated MMCs from 22 myeloma cases revealed 10 cases with active XBP-1, who also showed significantly poorer survival (p < 0.05), suggesting that chaperone expression protects MMCs from apoptosis, thereby allowing tumor cell expansion.