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首页> 外文期刊>Journal of Cancer >Heterogeneity of p53-pathway Protein Expression in Chemosensitive Chronic Lymphocytic Leukemia: A Pilot Study
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Heterogeneity of p53-pathway Protein Expression in Chemosensitive Chronic Lymphocytic Leukemia: A Pilot Study

机译：化学敏感性慢性淋巴细胞白血病中p53途径蛋白表达的异质性：一项初步研究。

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The presence of p53-pathway dysfunction in chronic lymphocytic leukemia (CLL) can be used to identify patients with chemotherapy-refractory disease. Therapeutic responses are known to vary between patients with chemosensitive CLL and may relate to differences in p53-pathway activity. We hypothesized that the magnitude or type of p53-pathway protein expression is heterogeneous in patients with chemosensitive disease and could associate with white cell responses. In this pilot study, changes in p53 and its transcriptional targets, p21/waf1 and MDM2 were analyzed by immunoblotting and densitometry in CLL cells from 10 patients immediately prior to the start of chemotherapy, and after culture for 24 hours (h) with fludarabine (n=7) or chlorambucil (n=3). The in vitro response was also compared to that in vivo in circulating cells pre-treatment, and at 24h and 96h of chemotherapy. Disease responses were evident in all patients after the first treatment-cycle. Significant p53 induction was observed in CLL cells treated in vitro and in vivo. Greater heterogeneity in the expression-intensity was observed in vivo (σ2=45.15) than in vitro (σ2=1.33) and the results failed to correlate (r2=0.18, p=0.22). p21/waf1 and MDM2 expression-profiles were also dissimilar in vitro and in vivo. Higher in vivo (but not in vitro) responses associated with changes in white cell count (p=0.026). Thus, heterogeneity of p53-pathway activity exists in chemosensitive CLL; in unselected patients, in vivo changes do not correlate with those in vitro, but may associate with post-treatment white cell responses.
机译：慢性淋巴细胞性白血病（CLL）中p53通路功能障碍的存在可用于鉴定患有化疗难治性疾病的患者。已知对化学敏感的CLL患者的治疗反应会有所不同，并且可能与p53途径活性的差异有关。我们假设p53通路蛋白表达的大小或类型在化学敏感性疾病患者中是异质的，并且可能与白细胞反应相关。在这项前期研究中，在即将开始化疗之前以及在与氟达拉滨培养24小时（h）后，通过免疫印迹和光密度法对10位患者的CLL细胞中的p53及其转录靶，p21 / waf1和MDM2的变化进行了分析。 n = 7）或苯丁酸氮芥（n = 3）。还比较了循环细胞预处理，化疗后24h和96h的体外反应与体内反应。在第一个治疗周期后，所有患者的疾病反应均很明显。在体外和体内处理的CLL细胞中观察到明显的p53诱导。体内（σ2= 45.15）的表达强度比体外（σ2= 1.33）的表达强度具有更大的异质性，并且结果没有相关性（r 2 = 0.18，p = 0.22）。 p21 / waf1和MDM2的表达谱在体外和体内也不同。与白细胞计数变化相关的更高的体内（而非体外）反应（p = 0.026）。因此，化学敏感性CLL中存在p53途径活性的异质性。在未选择的患者中，体内变化与体外变化不相关，但可能与治疗后白细胞反应相关。

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