Nishimura S, Asou N, Suzushima H, Okubo T, Fujimoto T, Osato M, Yamasaki H, Lisha L, Takatsuki K
Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Leukemia. 1995 Apr;9(4):598-604.
Although the prototype of adult T cell leukemia (ATL) is an aggressive T cell neoplasm, ATL manifests four major clinical subtypes, acute, lymphoma, chronic, and smoldering. We studied the relationship between p53 gene alteration and clinical features in 34 patients with ATL, 14 acute type, 15 chronic type, and five crisis type transformed from chronic type. Using a polymerase chain reaction/single strand conformation polymorphism (PCR/SSCP) assay, followed by nucleotide sequencing, we detected mutations of the p53 gene in six of the 14 acute type patients, two of the five crisis type, and one of the 15 chronic type patients. Gene dosage studies, using PCR amplification and Southern blotting, showed loss of heterozygosity (LOH) of the p53 gene in four of the 14 acute type patients, two of the five crisis type, and one of 14 chronic type patients examined. These observations indicated that the frequency of p53 gene alterations in the acute and crisis types of ATL was markedly higher than that in chronic type, suggesting that p53 gene alteration plays a role in the disease progression of ATL.
尽管成人T细胞白血病（ATL）的原型是一种侵袭性T细胞肿瘤，但ATL表现出四种主要临床亚型，即急性型、淋巴瘤型、慢性型和冒烟型。我们研究了34例ATL患者（14例急性型、15例慢性型以及5例由慢性型转化而来的危象型）中p53基因改变与临床特征之间的关系。采用聚合酶链反应/单链构象多态性（PCR/SSCP）分析，随后进行核苷酸测序，我们在14例急性型患者中的6例、5例危象型患者中的2例以及15例慢性型患者中的1例检测到p53基因的突变。利用PCR扩增和Southern印迹进行的基因剂量研究显示，在检测的14例急性型患者中的4例、5例危象型患者中的2例以及14例慢性型患者中的1例存在p53基因杂合性缺失（LOH）。这些观察结果表明，急性型和危象型ATL中p53基因改变的频率明显高于慢性型，提示p53基因改变在ATL的疾病进展中起作用。
