BAL is a novel risk-related gene in diffuse large B-cell lymphomas that enhances cellular migration

Clinical risk factor models such as the International prognostic Index are used to identify diffuse large B-cell lymphoma (DLB-CL) patients with diffe rent risks of death from their diseases. To elucidate the molecular bases f or these observed clinical differences in outcome, differential display was used to identify a novel gene, termed BAL (B-aggressive lymphoma), which i s expressed at significantly higher levels in fatal high-risk DLB-CLs than in cured low risk tumors. The major BAL complementary DNA encodes a previou sly uncharacterized 88-kd nuclear protein with a duplicated N-terminal doma in homologous to the non- histone portion of histone-macroH2A and a C-termi nal alpha-helical region with 2 short coiled-coil domains. Of note, the BAL N-terminus and secondary structure resemble those of a recently identified human protein, KIAA1268. In addition, both BAL and KIAA1268 map to chromos ome 3q21, further suggesting that these genes belong to a newly identified family. BAL is expressed at increased levels in DLB-CL cell lines with an a ctivated peripheral B cell, rather than a germinal center cell, phenotype. This observation and the characteristic dissemination of high risk DLB-CLs prompted studies regarding the role of BAL in B-cell migration. In classica l transwell assays, stable BAL-overexpressing B-cell lymphoma transfectants had significantly higher rates of migration than vector-only transfectants , indicating that the risk-related BAL gene promotes malignant B-cell migra tion. (Blood. 2000;96:4328-4334) (C) 2000 by The American Society of Hemato logy.