儿童急性白血病细胞视网膜母细胞瘤蛋白的表达及临床意义

本研究检测视网膜母细胞瘤蛋白（retinoblastoma protein，pRb）在不同类型儿童急性白血病细胞中的表达，并探讨其表达水平与细胞周期、危险度、微小残留病（minimal residual disease，MRD）监测、预后等临床诊断治疗监测指标的关系。对89例初发小儿急性白血病患者（包括25例AML，10例T-ALL，54例B-ALL）及7例正常对照骨髓标本，采用流式细胞术（FCM）分别检测治疗前后视网膜母细胞瘤蛋白的表达情况．并对部分病例进行细胞周期分析。结果表明：①流式细胞术检测pRb的表达准确直观；②在各种类型的急性白血病中pRb的高水平表达具有普遍性，同一患儿白血病细胞pRb的表达明显高于非白血病细胞，在不同类型的急性白血病中pRb均有缺失表达；③pRb的表达水平与白血病细胞的细胞循环周期可能存在一定的相关性，pRb表达阳性的B-ALL中处于G1期的白血病细胞数显著高于pRb表达阴性的病例（92％ vs 77％）；④B-ALL中，MRD阳性组pRb的表达量明显低于阴性组，且差值有统计学意义（P〈0．05），并且治疗前后非白血病细胞的pRb表达水平是稳定的；⑤pRb的表达量与B—ALL早期治疗预后之间存在一定相关性，B-ALL预后不良组pRb的表达量低于预后良好组（P〈0．05）。结论：pRb在儿童急性白血病细胞中存在高水平表达或缺失等异常形式的表达差异，pRb的表达与白血病细胞的细胞周期、MRD监测、早期治疗反应的预后评价等存在相关性，对于B-ALL的治疗监测及预后评估具有指导意义。

Expression of Retinoblastoma Protein in Child Acute Leukemia Cells and Its Clinical Significance

The research was aimed to detect the expression levels of retinoblastoma protein (pRb) in child acute leukemia cells, and to explore its possible association with leukemia cells cycle, the risk of disease, minimal residual disease (MRD) monitoring and prognosis of B-ALL. Flow cytometry (FCM) was used to detect the expression of pRb in 89 cases of acute leukemia (including 25 AML, 10 T-ALL and 54 B-ALL) and bone marrows from 7 normal children (control group). Meanwhile the cell cycle in some cases was analyzed. The results showed that (1) the FCM could accurately detect the expression of pRb in acute leukemia cells; (2) the high level of pRb expression was frequent in all types of child acute leukemias. In the same case, the expression of pRb was significantly increased in leukemia cells when compared with non-leukemia cells. And no detectable pRb protein was found in partial cases of acute leukemia; (3) there was a close relation between expression of pRb and the cell cycle of leukemia cells, the number of G(1) phase cells in pRb positive case of B-ALL was more than that in pRb negative case (92% vs 77%); (4) in B-ALL, the level of pRb expression in MRD positive group was significantly lower than that in MRD negative group (P < 0.05), but pRb expression was stable in non-leukemia cells during therapy; (5) pRb expression was related to the early response to therapy in B-ALL, the expression of pRb was significantly increased in sensitive group when compared with insensitive group (P < 0.05). It is concluded that high level or absence of pRb expression can be found in child acute leukemia cells. The expression of pRb is positively related to cell cycle of leukemia cells, MRD monitoring and the early response to therapy. In short, the detection of pRb expression level can guide the therapy and the evaluation of prognosis in B-ALL.