Invernizzi R, Pecci A, Bellotti L, Ascari E
Università di Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy.
Leuk Lymphoma. 2001 Jul;42(3):481-9. doi: 10.3109/10428190109064605.
We analysed by immunocytochemistry the expression of p53, bcl-2 and ras proteins in bone marrow blasts from 59 patients with acute leukaemia (AL), 36 myeloid (AML) and 23 lymphoid (ALL), and from 22 patients with myelodysplastic syndrome (MDS); our aim was to examine if abnormalities in their expression were associated with peculiar biological and clinical findings, or with an altered apoptosis rate, as measured by TUNEL technique. The oncoproteins were expressed with extreme variability, without significant differences among the various morphological or immunological AL subtypes. The mean percentages of bcl-2+ blasts were significantly higher in AML than in MDS (p = 0.01), and in MDS with bone marrow blastosis than in the forms without excess of blasts (p = 0.007). The lowest percentages of apoptotic cells were observed in ALL (mean 1%, p = 0.006), whereas in MDS the apoptotic index was higher (16.7%) than in AML (8.6%) and than in the normal controls (10.8%). but the difference tended to be statistically significant only for cases of refractory anaemia. Whereas in AML and MDS the apoptotic rate was independent of the oncoprotein expression, in ALL there was a significant linear relationship between TUNEL and ras positivity (p = 0.01). Among AML patients treated with intensive polychemotherapy, no differences were observed in oncoprotein expression and apoptotic rate between responders and resistant cases. In conclusion, our data are in agreement with the hypothesis that decreased apoptosis and enhanced cell survival are associated with AL, whereas a high level of apoptosis may be responsible for the ineffective hematopoiesis in MDS; abnormal expression of oncoproteins, even if not strictly related to apoptosis level, may influence disease behaviour.
我们采用免疫细胞化学方法分析了59例急性白血病（AL）患者（36例髓系白血病（AML）和23例淋巴细胞白血病（ALL））以及22例骨髓增生异常综合征（MDS）患者骨髓原始细胞中p53、bcl-2和ras蛋白的表达情况；我们的目的是检查这些蛋白表达异常是否与特殊的生物学和临床特征相关，或者与通过TUNEL技术检测的凋亡率改变相关。这些癌蛋白的表达具有极大的变异性，在各种形态学或免疫学分型的AL亚型之间无显著差异。AML中bcl-2阳性原始细胞的平均百分比显著高于MDS（p = 0.01），并且在伴有骨髓原始细胞增多的MDS中高于无原始细胞增多的类型（p = 0.007）。凋亡细胞百分比最低的是ALL（平均1%，p = 0.006），而MDS的凋亡指数（16.7%）高于AML（8.6%）和正常对照（10.8%）。但仅难治性贫血病例的差异有统计学意义的趋势。在AML和MDS中，凋亡率与癌蛋白表达无关，而在ALL中，TUNEL与ras阳性之间存在显著的线性关系（p = 0.01）。在接受强化联合化疗的AML患者中，反应者与耐药者之间在癌蛋白表达和凋亡率方面未观察到差异。总之，我们的数据与以下假设一致，即凋亡减少和细胞存活增强与AL相关，而高水平凋亡可能是MDS中造血无效的原因；癌蛋白的异常表达即使与凋亡水平无严格关联，也可能影响疾病行为。
