Using UCH-L1 to Identify Patients with Aggressive Germinal Center Diffuse Large B-Cell Lymphoma

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Andrew Feldman, M.D., Department of Pathology and Laboratory Medicine author on the paper
Andrew Feldman, M.D., Department of Pathology and Laboratory Medicine author on the paper

Gene expression profiling has identified two major subclasses of diffuse large B-cell lymphoma. Cases resembling  (GCB-DLBCL) generally occur in younger patients, have a distinct molecular pathophysiology, and have improved outcomes compared with those similar to activated post-germinal center cells (ABC-DLBCL).

In a previous study, Mayo Clinic researchers found that the ubiquitin hydrolase UCH-L1 is frequently overexpressed in mature B-cell malignancies and is a potent oncogene in mice. However, the cause for its overexpression in lymphoma, and whether it impacts the outcome of patients with DLBCL is unknown.

In a new study published in the journal Blood, Mayo Clinic researchers demonstrate that UCH-L1 reflects germinal center in lymphoma and is an oncogenic biomarker of aggressive GCB-DLBCL.

Researchers found that UCH-L1 is specifically induced in germinal center B-cells in mice and humans, and that its expression correlates highly with the GCB subtype in DLBCL. The study also indicated that UCH-L1 cooperates with BCL6 in a mouse model of germinal center B-cell lymphoma, but not with the development of multiple myeloma derived from post-germinal center cells.

Despite the typically good outcomes of GCB-DLBCL, increased UCHL1 identifies a subgroup with early relapses independent of MYC expression, suggesting biologic diversity in this subset of disease. Consistent with this, forced Uchl1 overexpression had a substantial impact on gene expression in germinal center B-cells including pathways of cell cycle progression, cell death and proliferation, and DNA replication.

These results demonstrate a novel role for UCH-L1 outside of the nervous system and suggest its potential use as a biomarker and therapeutic target in DLBCL.

Kelley Luedke (@kschrib)

Kelley Luedke

Kelley Luedke is a Marketing Channel Manager at Mayo Clinic Laboratories. She is the principle editor and writer of Insights and leads social media and direct marketing strategy. Kelley has worked at Mayo Clinic since 2013. Outside of work, you can find Kelley running, traveling, playing with her kitty, and exploring new foods.