Miwa H, Kita K, Saya H, Otsuji A, Masuya M, Nishii K, Morita N, Takakura N, Ohishi K, Nasu K
Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
Leuk Res. 1992 Nov;16(11):1105-12. doi: 10.1016/0145-2126(92)90049-d.
We have investigated alterations of the p53 gene in human leukemias by polymerase chain reaction-mediated restriction fragment length polymorphism analysis. This method detects the codon 72 polymorphism of the p53 gene, allowing identification of loss of heterozygosity (LOH) of the p53 gene. In this study, at least two specimens were obtained from each patient to compare the allele status at different points of clinical course. Of 21 cases examined 7 were heterozygous at this polymorphic site and were evaluable for LOH study. Only one patient of Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) lost the heterozygosity in the specimen of her last relapse. Leukemic cells from her repeated relapses including the last one revealed to have the clonally rearranged immunoglobulin H chain gene of the same size, indicating that alteration of the p53 gene in this patient might account for the lethal relapse as a clonal evolution event. Northern-blot analysis of the p53 gene showed that one case of CD7(+) ALL had altered p53 mRNA. Overall, it is demonstrated that alterations of the p53 gene might be involved in the pathogenesis or progression of at least some human leukemias, although the alterations in leukemias seemed to be not as frequent as in solid tumors.
我们通过聚合酶链反应介导的限制性片段长度多态性分析，研究了人类白血病中p53基因的改变。该方法可检测p53基因第72密码子的多态性，从而识别p53基因杂合性缺失（LOH）。在本研究中，从每位患者至少获取两份标本，以比较临床病程不同阶段的等位基因状态。在检测的21例病例中，7例在该多态性位点为杂合子，可用于LOH研究。仅1例费城染色体阳性急性淋巴细胞白血病（ALL）患者在最后一次复发的标本中出现杂合性缺失。她多次复发（包括最后一次）的白血病细胞显示具有相同大小的克隆性重排免疫球蛋白H链基因，表明该患者p53基因的改变可能作为一种克隆进化事件导致致命性复发。对p53基因的Northern印迹分析显示，1例CD7(+) ALL患者的p53 mRNA发生改变。总体而言，结果表明p53基因的改变可能参与了至少部分人类白血病的发病机制或进展，尽管白血病中的改变似乎不如实体瘤中频繁。
