Umadome H, Uchiyama T, Hori T, Tamori S, Motoi T, Araki K, Uchino H
First Division of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
J Clin Invest. 1988 Jan;81(1):52-61. doi: 10.1172/JCI113309.
Human T cell leukemia/lymphoma (T-lymphotropic) virus type I (HTLV-I) infection has been considered to be closely associated with the leukemogenesis of adult T cell leukemia (ATL), in which interleukin 2 (IL-2) receptors are abnormally expressed. In this study, however, Southern blot analysis revealed no gross rearrangement or obvious amplification of the IL-2 receptor gene in ATL leukemic cells, indicating that abnormal IL-2 receptor expression in ATL is not due to the structural change of its gene. Hence, we studied the expression of the IL-2 receptor and HTLV-I at the RNA level during short-term cultures of leukemic cells from 9 ATL patients. Cytoplasmic dot hybridization and Northern hybridization revealed that fresh leukemic cells from seven of nine patients expressed a small amount of IL-2 receptor mRNA but HTLV-I RNA was undetectable in all cases. After cultures for up to 7 d, both IL-2 receptor mRNA and HTLV-I RNA (including pX message) expression concomitantly increased, whereas the amounts of other cellular genes, except for beta-actin, did not. The increases in their RNA expression were inhibited by early addition (within 12 h after the beginning of the culture) of cycloheximide, indicating that these increases are mediated by newly synthesized protein(s). These results strongly suggested that IL-2 receptor expression is closely associated with HTLV-I expression in leukemic cells from ATL patients.
人类T细胞白血病/淋巴瘤(T淋巴细胞嗜性)病毒I型(HTLV-I)感染被认为与成人T细胞白血病(ATL)的白血病发生密切相关,在ATL中白细胞介素2(IL-2)受体异常表达。然而,在本研究中,Southern印迹分析显示ATL白血病细胞中IL-2受体基因无明显重排或明显扩增,这表明ATL中IL-2受体的异常表达并非因其基因结构改变所致。因此,我们研究了9例ATL患者白血病细胞短期培养过程中IL-2受体和HTLV-I在RNA水平的表达。细胞质斑点杂交和Northern杂交显示,9例患者中有7例的新鲜白血病细胞表达少量IL-2受体mRNA,但所有病例中均未检测到HTLV-I RNA。培养长达7天后,IL-2受体mRNA和HTLV-I RNA(包括pX信息)的表达同时增加,而除β-肌动蛋白外的其他细胞基因的量未增加。它们RNA表达的增加在培养开始后12小时内早期添加环己酰亚胺可被抑制,这表明这些增加是由新合成的蛋白质介导的。这些结果强烈提示,ATL患者白血病细胞中IL-2受体表达与HTLV-I表达密切相关。