肿瘤抑制基因p53及其拮抗癌基因mdm2在急性白血病发病机制中的作用(英文)

Role of Tumor Suppressor Gene p53 and Its Antagonist Oncogene mdm2 in Pathogenesis of Acute Leukemia

研究了41例急性白血病患者以及两个白血病细胞系K051与HL-60中肿瘤抑制基因p53及其拮抗基因mdm2的改变和相互关系。研究结果如下:①在可分析结果的33例急性白血病中,13例有染色体异常,但未发现与上述两个癌基因有关的12号或17号染色体异常;②41例急性白血病中8例可能有p53基因突变,发生率为19.5％,高于文献中同类报道的结果。p53基因点突变与急性白血病的FAB分型以及患者的预后无明显关系,主要发生在染色体核型正常的急性白血病患者;③在41例急性白血病患者以及K051和HL-60两个细胞系中未检出mdm2基因的扩增;④发现51.2％(21/41)的急性白血病患者有较高水平的mdm2基因的表达,其中3例同时有p53基因突变(3/21);K051细胞系mdm2基因表达水平较低,而HL-60细胞系的表达水平则较高。mdm2基因的表达水平与白血病FAB分型、染色体异常及p53基因点突变无明显关系,与急性白血病的预后有一定的关系。根据上述结果进行了讨论,认为急性白血病中,虽然p53基因的突变率较低,但是由于其拮抗基因mdm2的过高表达,p53基因的失活仍然可能是急性白血病发生和发展的机制之一。

The status of the tumor suppressor gene p53 and its antagonist oncogene mdm2 and the rela-tions betvveen them were studied in 41 acute leukemia patients and two Ieukemic cell lines K051 and HL-60. Our results demonstrated that: ① Chromosome abnormalities were seen in 13 of 33 leukemia patients, but none of them involved 17p and 12q. ② No amplification of mdm2 gene were found in all the 41 patients and two celi lines when detected with Southern blot. ③By using RT- PCR/SSCP, mutations of p53 gene were detected in 8 out of 41 acute leukemia patients; the incidence of the mutations was higher than those reported in literatures. p53 gene mutations showed no relations to FAB subtypes of acute leukemia and prognosis of the patients. ④By using RT- PCR, over- expression of mdm2 gene was detected in 21 patients out of the 41 patients and in cell line HL - 60 but not in K051. Over - expression of mdm2 gene has relation to the prognosis of the patients but not to FAB subtypes of leukemia and p53 gene mutations. It was concluded and confirmed from our results that over - expression of mdm2 gene is frequent in acute leukemia, which means inactivation of p53 gene is one of the mechanisms in the initiation and development of acute leukemia al-though mutations of p53 are less frequent in acute leukemia than that in solid tumors.