The growth-regulatory role of B-cell-specific activator protein in NZB malignant B-1 cells

Abstract

 The transcription factor B-cell-specific activator protein (BSAP) plays an important role in B-cell development. We explored the involvement of BSAP in the growth regulation of malignant B-1 cells derived from the NZB murine model of human chronic lymphocytic leukemia. BSAP protein was found in normal B-2 cells, elevated in normal B-1 cells, and highest in NZB malignant B-1 cells. When these malignant B-1 cells were treated with antisense oligonucleotides for BSAP, their growth was inhibited with a G2/M phase arrest. In contrast, B cell lines that did not appear to be of B-1 origin (IgG⁺/B220⁺/BSAP^low) were unaffected by treatment with antisense BSAP oligonucleotides. Centrifugal elutriation experiments showed that BSAP mRNA was expressed at the highest levels in the G2/M phases in malignant B-1 cells. Treatment with demecolcine (Colcemid), a known mitotic blocker, resulted in a decrease in the level of BSAP gene expression in malignant B-1 cells, further demonstrating links between BSAP expression and successful G2/M transition in the cell cycle. These data suggest a correlation between BSAP and the development of B-1 malignancy, perhaps through the regulation of cell-cycle progression.