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Blood, 15 December 2000, Vol. 96, No. 13, pp. 4328-4334
NEOPLASIA
BAL is a novel risk-related gene in diffuse large
B-cell lymphomas that enhances cellular migration
Ricardo C. T. Aguiar,
Yoshihiro Yakushijin,
Samir Kharbanda,
Ravi Salgia,
Jonathan A. Fletcher, and
Margaret A. Shipp
From the Department of Adult Oncology, Dana-Farber
Cancer Institute, and the Department of Pathology, Brigham and Women's
Hospital, Harvard Medical School, Boston, MA.
Clinical risk factor models such as the International Prognostic
Index are used to identify diffuse large B-cell lymphoma (DLB-CL)
patients with different risks of death from their diseases. To
elucidate the molecular bases for these observed clinical differences in outcome, differential display was used to identify a novel gene,
termed BAL (B-aggressive
lymphoma), which is expressed at significantly higher
levels in fatal high-risk DLB-CLs than in cured low-risk tumors. The
major BAL complementary DNA encodes a previously
uncharacterized 88-kd nuclear protein with a duplicated N-terminal
domain homologous to the nonhistone portion of histone-macroH2A and a
C-terminal 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 chromosome 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 activated peripheral B cell, rather than a germinal center B 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 classical 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 migration.
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