Bortezomib induces heme oxygenase-1 expression in multiple myeloma.

ABSTRACT

Multiple myeloma (MM) is a progressive malignant disorder characterized by accumulation of plasma cells in the bone marrow. MM remains an incurable disease with a 5-y survival rate of approximately 40%. While clinical response rates to first line chemotherapeutics are high, disease relapse is inevitable, and occurs because a small fraction of the original myeloma cells appear to be resistant to treatment. Heme oxygenase-1 (HO-1) is an Nrf2 transcription factor-regulated gene that is commonly induced following oxidative stress and cellular injury, functioning to decrease oxidative stress and inflammatory responses, protecting against apoptosis and altering the cell cycle. We and others have highlighted the role of HO-1 in providing cellular protection against chemotherapeutic drugs in a number of cancer cells, which we have highlighted here in this Extra View. Furthermore, we explored the expression of HO-1 in multiple myeloma cells in response to the key anti-myeloma drugs bortezomib and lenalidomide. We show here for the first time that bortezomib increases HO-1 expression in a time- and concentration-dependent manner. Moreover, we also observe that HO-1 is increased in lenalidomide-resistant MM cell lines. Altogether, we highlight a possible role for HO-1 in basal and acquired chemoresistance in MM.