ALK-negative anaplastic large cell lymphoma is sensitive to bortezomib through Noxa upregulation and release of Bax from Bcl-2

摘要

Clinical outcome in anaplastic large cell lymphoma (ALCL), especially in systemic anaplastic lymphoma kinase (ALK)-negative ALCL is frequently poor, despite intensive therapy regimens including CHOP (vincristine, doxorubicin, cyclophosphamide and prednisone), with or without etoposide. Although promising results have been obtained with targeted therapies such as brentuximab vedotin, alemtuzumab and/or stem cell transplantation, alternative therapies are needed which can improve patient outcome.~(~(1),~(2))Recent studies have demonstrated that expression levels of many NF-B regulated anti-apoptotic proteins are elevated in ALCL.~(~(3)~(5)) NF-B activity can be inhibited by the proteasome inhibitor bortezomib, resulting in induction of apoptosis.~(~(6)) Bortezomib has shown remarkable preclinical anti-tumor activity in various types of cancer and was approved by the FDA for the treatment of multiple myeloma and mantle cell lymphoma. In the present study, we therefore investigated if bortezomib can induce apoptosis of primary lymphoma cells from ALK-negative and ALK-positive ALCL patients and in ALCL cell lines.