Romidepsin overcomes cell adhesion-mediated drug resistance in multiple myeloma cells

摘要

Multiple myeloma (MM) is a malignant hematopoi-etic disease that remains incurable. Therapeutic strategies for this disease have been rapidly progressing based on the development of new drugs, including proteasome inhibitors, immunomodulatory agents, antibodies and small molecular compounds such as histone deacetylase inhibitors (HDIs); however, drug resistance remains a major challenge [1]. It is well known that cell adhesion-mediated drug resistance (CAM-DR) occurs when MM cells interact with stromal cells [2]. Specifically, MM cells express surface adhesion receptor molecules which bind with corresponding ligands on stromal cells. Such interaction results in protection of MM cells from the cyto-toxic effects of anti-myeloma drugs. We previously found that MM cells express various adhesion molecules, including CD29 (beta1-integrin), CD49d (alpha4-integrin, a sub-unit of VLA-4), CD54 (intercellular adhesion mole-cule-1), CD138 (syndecan-1), CD184 (CXC chemokine receptor-4), and CD44. Furthermore, among them CD49d was crucial for CAM-DR to conventional anti-myeloma drugs such as bortezomib and dexamethasone [3]. Thus, it is of great importance to suppress CD49d expression to overcome CAM-DR.