Targeted therapy of BCL6-dependent diffuse large B-cell lymphomas by heat-shock protein 90 inhibition

Abstract

Heat-shock protein (HSP)90 is a molecular chaperone involved in the proper folding and cellular transportation of many signaling proteins that are deregulated in lymphoma. HSP90 inhibition results in proteasomal degradation of these proteins, leading to antitumoral activity. Recent studies have focused on the use of HSP90 inhibitors as potential therapies for non-Hodgkin lymphoma. BCL6 plays a critical role in the pathogenesis of most diffuse large B-cell lymphoma (DLBCL), the most frequent non-Hodgkin lymphoma. The current study demonstrates that HSP90 forms a complex with BCL6, and inhibition of HSP90 with the drug PU-H71 selectively kills BCL6-positive DLBCL in animal models. These data support the use of HSP90 inhibitor PU-H71 for treating patients with BCL6-positive DLBCL.