Porwit-MacDonald A, Ivory K, Wilkinson S, Wheatley K, Wong L, Janossy G
Department of Clinical Immunology, Royal Free Hospital School of Medicine, London, UK.
Leukemia. 1995 Jul;9(7):1191-8.
The expression of bcl-2 protein that is involved in preventing apoptosis in hemopoietic and other cells was evaluated by quantitative flow cytometry in various subpopulations in the normal fetal bone marrow (FBM) and in different types of acute myelogenous leukemias (AML). In the FBM the highest bcl-2 levels (mean antibody binding capacity 51 x 10(3) molecules/cell) were found in CD34+ intermediate sized blasts and myeloblasts, while a CD34+ subset of CD10+ lymphoblasts had low bcl-2 content (8-10 x 10(3) molecules/cell) and the CD34-, CD10+ lymphoblasts were, as expected from previous studies, bcl-2- (< 5 x 10(3) molecules/cell). Variable levels of bcl-2 (5.1-222 x 10(3)) were found in 43 tested cases of AML. The bcl-2 levels decrease with granulocytic and monocytic differentiation and, accordingly, cases of AML with M1 and M2 features showed significantly higher mean bcl-2 levels than the leukemias with promyelocytic (M3) or myelo-monocytic (M4/M5) features. Nevertheless, in seven cases of AML the bcl-2 levels were higher than seen in the normal FBM cells and none of these patients remain in remission after 2 years. Furthermore, in several AML cases intraclonal heterogeneity was observed. The undifferentiated smaller blasts with Class-IIdim display had higher bcl-2 content than the more differentiated larger blasts with more granular side scatter and Class-bright expression. In the same subsets of AML blasts the proliferative S-G2-M fractions showed a reciprocal correlation to bcl-2 content. Thus the higher bcl-2 levels may give a survival advantage and confer some degree of drug resistance to the least differentiated blast populations. The multi-parameter analysis described in this paper, including a combined bcl-2 and cytokinetic analysis of phenotypically defined subgroups of AML blasts, may detect early population shifts during relapse and also guide combination drug therapy.
通过定量流式细胞术评估了参与防止造血细胞和其他细胞凋亡的bcl-2蛋白在正常胎儿骨髓（FBM）的各种亚群以及不同类型急性髓系白血病（AML）中的表达。在FBM中，CD34+中等大小的原始细胞和成髓细胞中bcl-2水平最高（平均抗体结合能力为51×10³个分子/细胞），而CD10+淋巴母细胞的CD34+亚群bcl-2含量较低（8 - 10×10³个分子/细胞），并且如先前研究所预期的，CD34-、CD10+淋巴母细胞bcl-2阴性（<5×10³个分子/细胞）。在43例检测的AML病例中发现了不同水平的bcl-2（5.1 - 222×10³）。bcl-2水平随着粒细胞和单核细胞分化而降低，因此，具有M1和M2特征的AML病例的平均bcl-2水平显著高于具有早幼粒细胞（M3）或粒-单核细胞（M4/M5）特征的白血病。然而，在7例AML病例中，bcl-2水平高于正常FBM细胞，并且这些患者中没有一人在2年后仍处于缓解状态。此外，在一些AML病例中观察到克隆内异质性。具有IIdim类未分化较小原始细胞的bcl-2含量高于具有更多颗粒侧向散射和明亮类表达的分化程度更高的较大原始细胞。在AML原始细胞的相同亚群中，增殖的S - G2 - M部分与bcl-2含量呈负相关。因此，较高的bcl-2水平可能赋予生存优势，并使分化程度最低的原始细胞群体具有一定程度的耐药性。本文所述的多参数分析，包括对AML原始细胞表型定义亚群进行bcl-2和细胞动力学联合分析，可能检测复发期间早期的群体变化，并指导联合药物治疗。
