 Diffuse large B-cell lymphomas DLBCL have been molecularly sub-classified into germinal center like B-cell GCB and activated B-cell like ABC DLBCL. Clinically, the ABC subtype has a significantly higher rate of drug resistance and lower survival. The ABC subtype has overexpression of nuclear factor-kappa B NF-kB with transcriptional activation of B cell lymphoma 2 bcl-2, which may account for the drug resistance. The ability of NF-kB to inhibit responses to cancer therapeutic agents may also contribute to the refractory clinical behavior of ABC subtype, and inhibition of NF-kB can synergize with the chemotherapy to kill tumor cells. This protocol aims to study the affect of NF-kB inhibition, through proteasome inhibition by PS-341, on response to PS-341 and PS-341 with EPOCH chemotherapy in DLBCL. It will also assess the affect of PS-341 on NF-kB and BCL-2 tumor expression by microarray, and provide information on the specificity of PS-341. 