Marks D I, Kurz B W, Link M P, Ng E, Shuster J J, Lauer S J, Carroll D, Brodsky I, Haines D S
Department of Medicine, Allegheny University of the Health Sciences, Philadelphia, PA 19102, USA.
J Clin Oncol. 1997 Mar;15(3):1158-62. doi: 10.1200/JCO.1997.15.3.1158.
To determine whether potential alteration in p53 function through p53 gene mutation or mdm-2 overexpression correlates with early treatment failure in childhood acute lymphoblastic leukemia (ALL).
Diagnostic marrow samples from 34 children were analyzed for p53 gene alterations by western blot and SSCP/DNA sequence analysis and for mdm-2 overexpression by western blot analysis. These samples were derived from two groups of children with ALL: 17 good outcome patients who are in long-term continuous complete remission and 17 poor outcome patients who did not achieve a complete remission or relapsed within 6 months of achieving remission.
Two children within the poor outcome group were found to have p53 gene mutations. Furthermore, five poor outcome patients were shown to have greater than 10-fold overexpression of mdm-2 protein compared with the mean level of mdm-2 protein measured in the good outcome group. Aberrant p53 protein expression was found in only one good outcome patient, whereas no good outcome children were found to have elevated levels (> 10-fold) of mdm-2 protein.
We show for the first time that potential alteration in p53 function in childhood ALL is more common (P = .036) in cases of early treatment failure than in children who remain in long-term continuous remission.
确定通过p53基因突变或mdm-2过表达引起的p53功能潜在改变是否与儿童急性淋巴细胞白血病（ALL）的早期治疗失败相关。
采用蛋白质印迹法和单链构象多态性/DNA序列分析法对34例儿童的诊断性骨髓样本进行p53基因改变分析，采用蛋白质印迹分析法对mdm-2过表达进行分析。这些样本来自两组ALL患儿：17例预后良好的患者，处于长期持续完全缓解状态；17例预后不良的患者，未达到完全缓解或在达到缓解后6个月内复发。
在预后不良组中发现2例患儿存在p53基因突变。此外，与预后良好组中测量的mdm-2蛋白平均水平相比，5例预后不良患者的mdm-2蛋白过表达超过10倍。仅在1例预后良好的患者中发现异常p53蛋白表达，而未发现预后良好的儿童mdm-2蛋白水平升高（>10倍）。
我们首次表明，儿童ALL中p53功能的潜在改变在早期治疗失败的病例中比长期持续缓解的儿童更常见（P = 0.036）。
