Functional Link Between Heat Shock Protein Hsp90alpha And Sirtuin 1 (Sirt1) In The Pathogenesis Of Diffuse Large B Cell Lymphoma

Diffuse large B-cell lymphomas (DLBCL) are heterogenous tumors. A large subset of DLBCL is reliant on B-cell receptor activity ('BCR'-DLBCLs). Additional subset of tumors that does not exhibit addiction to BCR signaling features transcriptional program is associated with increased oxidative phosphorylation ('OxPhos'-DLBCLs, Blood 2005; 105: 1851-61). These OxPhos tumros are resistant to BCR inhibition and remain functionally poorly defined. We and others found that OxPhos-DLBCLs, compared to BCR subtype, exhibit overexpression of heat shock protein HSP90alpha (Br J Haematol 2009; 144: 358-66). Expression of multiple heat shock proteins is regulated by the activity of a stress-responsive, acetylation-dependent transcription factor HSF1. Acetylation blocks, whereas deacetylation by sirtuins increases HSF1 activity. However, molecular mechanisms responsible for increased HSP90alpha expression in OxPhos-DLBCLs remain unknown.