儿童急性白血病PCNA和P53及Bcl-2蛋白表达及其临床意义

Expression and Clinical Significance of PCNA, p53 and Bcl-2 Protein in Bone Marrow Cells in Children with Acute Leukemia

目的探讨儿童急性白血病(AL)骨髓细胞增殖细胞核抗原(PCNA)与抗凋亡基因P53、Bcl-2蛋白的表达及其与临床化疗和预后的关系。方法应用S-P免疫组织化学方法检测59例儿童AL骨髓穿刺标本,分别应用PCNA、P53、Bcl-2单克隆抗体进行检测。选择15例正常骨髓穿刺组织标本作为对照。结果PCNA、Bcl-2、P53在AL初治病例中的表达与对照组,未缓解组与缓解组比较均有显著性差异(P<0.05);PCNA表达复发难治组与对照组比较无显著性差异,与化疗敏感性有关,阳性表达组与阴性表达组,6周内缓解率有显著性差异(P<0.05),而3年以上无病生存率比较无差异(P>0.05);P53、Bcl-2表达复发难治组显著高于对照组,高表达者,化疗耐药,缓解率低,二者共同阳性者,不易缓解,提示预后不良。结论PCNA阳性表达者缓解率高,与长期预后无关。Bcl-2、P53阳性表达者缓解率低,与长期预后有关,二者可作为判断化疗效应及预后的分子生物学指标;PCNA、P53、Bcl-2基因以不同的途径参与儿童AL的发生过程,三者联合检测判断预后有更大的临床价值。

Objective To investigate the relationship between the expressions of proliferating cell nuclear antigen (PCNA), p53 and Bcl-2 protein and clinical chemothreapy, prognosis in bone marrow cells in children with acute leukemia (AL). Methods Immunohistochemical SP method was used to detect the expressions of PCNA, p53 and Bcl-2 in specimens of bone marrow puncture of 59 children with AL and 15 healthy children as control. Results There was a significant difference in the expressions of PCNA, p53 and Bcl-2 proteins between the initially treated patients and healthy subjects, and between the remission patients and non remission ones. There was not a significnat difference in PCNA expression between the refractory patients and healthy subjects, and PCNA expression was related to the chemotherapeutic sensitivity. There was a significant difference in the 6-week remission rate between the patients with and without PCNA expression, but there was no significant difference in the over 3 years survival rate without illness. The expression levels of Bcl-2 and p53 were significantly higher in the refractory patients than those in healthy subjects. The patients with the high expression of p53 and Bcl-2 were resistant to chemotherapy, low in the remission rate and poor in prognosis. Conclusion The AL patients with PCNA expression were higher in remission rate, and PCNA expression was not associated with long-term prognosis. The AL patients with the expression of p53 and Bcl-2 were lower in remission rate, and their expression was associated with long-term prognosis. Both p53 and Bcl-2 protein may serve as a molecular marker to predict chemotherapeutic sensitivity and prognosis. PCNA, p53 and Bcl-2 may be involved in the pathogenesis of child AL by various ways. It is more valuable for predicting prognosis to simultaneously detect the expression of PCNA, p53 and Bcl-2 proteins.