BRYOSTATIN 1-INDUCED MODULATION OF THE ACUTE LYMPHOBLASTIC-LEUKEMIA CELL-LINE REH

We have previously reported that the phorbol ester, 12-O-tetradecanoyl phorbol 13-acetate (TPA) induces further differentiation of the human acute lymphoblastic leukemia cell line Reh to a monocytoid B lymphocyt e stage. In the present study, we investigated the differentiating cap acity of another protein kinase C (PKC) activator, bryostatin 1 (bryo) . Reh cells were treated in vitro with TPA, bryo, or interferon-alpha. (IFN-alpha) for a period of 5 days during which cells were analyzed f or changes in growth patterns, morphology, cytochemistry, and surface phenotype. Bryo caused a dose-dependent growth inhibition of Reh cells . Morphologically, the treated cells expressed monocytoid features wit h development of filopodia and numerous vacuoles indicating phagocytic activity. Bryo induced similar phenotypic changes to TPA, including i nduction of CD11c, increased expression of CD22 and down-regulation of CD10 and CD19. Enzymatically, bryo, like TPA, induced tartrate-sensit ive acid phosphatase expression but failed to induce periodic acid Sch iff (PAS) and nonspecific esterase (NSE). Bryo inhibited the TPA actio n on NSE and CD10. IFN-alpha showed additive growth inhibitory and phe notypic effects to bryo. Collectively, our findings indicate that bryo is capable of inducing further differentiation of the Reh cells along the B cell lineage similar to those of TPA.