Expression of p53, bcl-2 and ras oncoproteins and apoptosis levels in acute leukaemias and myelodysplastic syndromes
Expression of p53, bcl-2 and ras oncoproteins and apoptosis levels in acute leukaemias and myelodysplastic syndromes
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DOI：
10.3109/10428190109064605
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发表时间：
2001-07-01
影响因子：
2.6
通讯作者：
Ascari, E
中科院分区：
文献类型：
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作者：
Invernizzi, R;Pecci, A;Ascari, E
我们用免疫细胞化学方法分析了59例急性白血病（AL）、36例髓系白血病（AML）、23例淋巴系白血病（ALL）和22例骨髓增生异常综合征（MDS）患者骨髓母细胞中p53、bcl-2和ras蛋白的表达；我们的目的是检查它们的异常表达是否与特殊的生物学和临床表现有关，或者与TUNEL技术测量的细胞凋亡率的改变有关。癌蛋白的表达具有极大的可变性，在各种形态学或免疫学AL亚型之间没有显著差异。AML中bcl-2+细胞的平均百分比明显高于MDS (p = 0.01)，有骨髓成母细胞的MDS中bcl-2+细胞的平均百分比明显高于无骨髓成母细胞的MDS （p = 0.007）。ALL的细胞凋亡率最低（平均1%，p = 0.006），而MDS的细胞凋亡指数（16.7%）高于AML（8.6%）和正常对照组（10.8%）。但只有在难治性贫血的情况下，这种差异才有统计学意义。在AML和MDS中，凋亡率与癌蛋白表达无关，而在ALL中，TUNEL与ras阳性呈显著的线性关系（p = 0.01）。在接受强化化疗的AML患者中，反应者和耐药者的肿瘤蛋白表达和凋亡率没有差异。综上所述，我们的数据支持AL与细胞凋亡减少和细胞存活增强相关的假设，而高水平的细胞凋亡可能是MDS患者造血功能低下的原因；癌蛋白的异常表达，即使与细胞凋亡水平没有严格的关系，也可能影响疾病行为。
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.