al-Katib A, Mohammad R M, Dan M, Hussein M E, Akhtar A, Pettit G R, Sensenbrenner L L
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201.
Exp Hematol. 1993 Jan;21(1):61-5.
The phorbol esters induce differentiation of chronic lymphocytic leukemia (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 cells from the peripheral blood of 13 patients with CLL were isolated and 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 phosphatase (ACP) and the co-expression of two hairy cell-associated surface antigens, CD22 and CD11c, by flow cytometry. Bryostatin 1 induced changes in shape and morphology similar to TPA, with adherence and increase in cell size, abundant cytoplasm and irregular cytoplasmic membrane. Both agents induced a statistically significant increase in the expression of CD22 and CD11c 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 was 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.
佛波酯可诱导慢性淋巴细胞白血病（CLL）细胞分化。然而，由于佛波酯也是肿瘤促进剂，这一观察结果在临床上的应用受到了阻碍。在本研究中，我们证明了另一种无肿瘤促进活性的蛋白激酶C激活剂对CLL细胞具有类似的作用。从13例CLL患者外周血中分离新鲜白血病细胞，在无（对照）或有苔藓抑素1或12 - O - 十四烷酰佛波醇13 - 乙酸酯（TPA）的情况下进行培养。然后在24、72和120小时后取细胞 aliquots，通过流式细胞术分析其形态变化、酸性磷酸酶（ACP）以及两种毛细胞相关表面抗原CD22和CD11c的共表达情况。苔藓抑素1诱导的形状和形态变化与TPA相似，表现为细胞贴壁、细胞大小增加、细胞质丰富且细胞质膜不规则。与对照相比，两种药物均诱导CD22和CD11c表达有统计学意义的增加（p < 0.0008）。这两种药物在这两种标志物的表达程度上没有显著差异。两种药物还诱导了抗酒石酸酸性磷酸酶（TRAP）。这些变化表明，苔藓抑素在诱导CLL细胞进一步分化为毛细胞阶段方面与TPA一样有效。
