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

The transcription factor B-cell-specific activator protein (BSAP) plays an important role in B-cell development. We explored the involvement of BSAP i n the growth regulation of malignant B-l cells derived from the NZB murine model of human chronic lymphocytic leukemia. BSAP protein was found in norm al B-2 cells, elevated in normal B-l cells, and highest in NZB malignant B- l cells. When these malignant B-l cells were treated with antisense oligonu cleotides 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-l origin (IgG(+)/B22 0(+)/BSAP(low)) were unaffected by treatment with antisense BSAP oligonucle otides. Centrifugal elutriation experiments showed that BSAP mRNA was expre ssed at the highest levels in the G2/M phases in malignant B-l cells. Treat ment with demecolcine (Colcemid), a known mitotic blocker, resulted in a de crease in the level of BSAP gene expression in malignant B-l 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 d evelopment of B-l malignancy, perhaps through the regulation of cell-cycle progression.