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 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. (Blood. 2000;96:4328-4334)
Aguiar
R C
RC
Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Yakushijin
Y
Y
Kharbanda
S
S
Salgia
R
R
Fletcher
J A
JA
Shipp
M A
MA
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D003001:Cloning, Molecular; D015972:Gene Expression Regulation, Neoplastic; D005796:Genes; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000473:pathology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases; D011993:Recombinant Fusion Proteins / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D012306:Risk; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D009363:Neoplasm Proteins; C418133:PARP9 protein, human; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D011065:Poly(ADP-ribose) Polymerases