Smith M
Pediatric Section, Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland 20892, USA.
J Immunother. 1997 Mar;20(2):89-100. doi: 10.1097/00002371-199703000-00001.
A large body of evidence supports the hypothesis that an infectious agent is involved in the etiology of acute lymphoblastic leukemia (ALL) in children in the 2-5-year age range. To explain these data, it has been proposed that some cases of pediatric ALL arise as a rare response to a common childhood infection, and that the leukemia-inducing potential of the agent is related to the timing of infection, with a greater leukemogenic effect for later infections compared with those occurring during infancy. An alternative model for the etiology of a subset of childhood ALL is proposed that places the critical infectious event during pregnancy rather than early childhood. In this model, the etiologic agent causes a primary infection in the mother that is transmitted to the fetus, and as a consequence of this in utero infection, the child is at increased risk of developing ALL before the age of 5 years. The characteristics that the causative infectious agent of childhood ALL occurring in the 2-5-year age range should possess include (a) ability to induce genomic instability; (b) specific effects on B lymphocytes and not on T lymphocytes; (c) higher rates of infection in regions with lower socioeconomic status; (d) limited general oncogenic potential; (e) minimal symptoms associated with the primary infection; and (f) ability to cross the placenta and infect the fetus, but not cause severe fetal abnormalities. A candidate virus meeting many of these criteria is the JC virus, a member of the polyomavirus family. Implications of the possible etiologic role of JC virus for some cases of childhood ALL (especially those with hyperdiploid leukemia cells) are discussed.
大量证据支持这样一种假说，即感染因子与2至5岁儿童急性淋巴细胞白血病（ALL）的病因有关。为了解释这些数据，有人提出，一些儿童ALL病例是对常见儿童感染的罕见反应，并且该病原体的致白血病潜力与感染时间有关，与婴儿期感染相比，后期感染的致白血病作用更大。有人提出了另一种儿童ALL亚组病因模型，该模型将关键感染事件置于孕期而非幼儿期。在这个模型中，病原体在母亲体内引发原发性感染，然后传播给胎儿，由于这种子宫内感染，儿童在5岁前患ALL的风险增加。2至5岁儿童ALL的致病感染因子应具备的特征包括：（a）诱导基因组不稳定的能力；（b）对B淋巴细胞而非T淋巴细胞有特定作用；（c）社会经济地位较低地区的感染率较高；（d）一般致癌潜力有限；（e）与原发性感染相关的症状轻微；（f）能够穿过胎盘并感染胎儿，但不会导致严重的胎儿异常。一种符合许多这些标准的候选病毒是JC病毒，它是多瘤病毒家族的成员。本文讨论了JC病毒可能的病因作用对一些儿童ALL病例（尤其是那些具有超二倍体白血病细胞的病例）的影响。
