Campos L, Rouault J P, Sabido O, Oriol P, Roubi N, Vasselon C, Archimbaud E, Magaud J P, Guyotat D
Centre de Transfusion Sanguine, Lyon, France.
Blood. 1993 Jun 1;81(11):3091-6.
The BCL-2 proto-oncogene encodes a mitochondrial protein that blocks programmed cell death. High amounts of bcl-2 protein are found not only in lymphoid malignancies, but also in normal tissues characterized by apoptotic cell death, including bone marrow. Using a monoclonal antibody to bcl-2 protein, we analyzed 82 samples of newly diagnosed acute myeloid leukemia. The number of bcl-2+ cells in each sample was heterogeneous (range, 0% to 95%), with a mean of 23%. The percentage of bcl-2+ cells was higher in M4 and M5 types, according to French-American-British classification, and in cases with high white blood cell counts. bcl-2 expression was also correlated with that of the stem cell marker CD34. In vitro survival of leukemic cells maintained in liquid culture in the absence of growth factors was significantly longer in cases with a high percentage of bcl-2+ cells. High expression of bcl-2 was associated with a low complete remission rate after intensive chemotherapy (29% in cases with 20% or more positive cells v 85% in cases with less than 20% positive cells, P < 10(-5)) and with a significantly shorter survival. In multivariate analysis, the percentage of bcl-2+ cells (or the blast survival in culture), age, and the percentage of CD34+ cells were independently associated with poor survival.
BCL-2原癌基因编码一种可阻止程序性细胞死亡的线粒体蛋白。不仅在淋巴系统恶性肿瘤中发现大量bcl-2蛋白，在以凋亡性细胞死亡为特征的正常组织（包括骨髓）中也能发现。我们使用针对bcl-2蛋白的单克隆抗体，分析了82例新诊断的急性髓系白血病样本。每个样本中bcl-2阳性细胞数量各异（范围为0%至95%），平均为23%。根据法美英分类法，M4和M5型以及白细胞计数高的病例中，bcl-2阳性细胞的百分比更高。bcl-2表达也与干细胞标志物CD34的表达相关。在无生长因子的液体培养中，bcl-2阳性细胞百分比高的病例中白血病细胞的体外存活时间显著更长。bcl-2高表达与强化化疗后的完全缓解率低相关（阳性细胞20%或更多的病例为29%，阳性细胞少于20%的病例为85%，P<10(-5)），且与生存期显著缩短相关。在多变量分析中，bcl-2阳性细胞的百分比（或培养中的原始细胞存活情况）、年龄和CD34阳性细胞的百分比与不良生存独立相关。
