BRYOSTATIN 1-INDUCED HAIRY-CELL FEATURES ON CHRONIC LYMPHOCYTIC-LEUKEMIA CELLS-INVITRO

The phorbol esters induce differentiation of chronic lymphocytic leuke mia (CLL) cells. Clinical use of this observation has been hampered by the fact that phorbol esters are also tumor promoters. In this study we demonstrate that another protein kinase C activator, without tumor promoting activity, has similar effects on CLL cells. Fresh leukemic c ells from the peripheral blood of 13 patients with CLL were isolated a nd cultured in the absence (control) or presence of Bryostatin 1 or 12 -0-tetradecanoylphorbol 13-acetate (TPA). Aliquots of cells were then analyzed after 24, 72 and 120 hours for morphological changes, acid ph osphatase (ACP) and the co-expression of two hairy cell-associated sur face antigens, CD22 and CD11c, by flow cytometry. Bryostatin 1 induced changes in shape and morphology similar to TPA, with adherence and in crease in cell size, abundant cytoplasm and irregular cytoplasmic memb rane. Both agents induced a statistically significant increase in the expression of CD22 and CD 1 lc compared with control (p<0.0008). There was no significant difference between the two agents in the degree of expression of these two markers. Both agents also induced ACP that wa s tartrate resistant (TRAP). These changes indicate that Bryostatin is as effective as TPA in inducing further differentiation of CLL cells to a hairy cell stage.