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Considerations on a possible viral etiology for B-precursor acute lymphoblastic leukemia of childhood
1Pediatric Section, Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland 20892, USA.
Insights
A novel model suggests prenatal infection may cause childhood acute lymphoblastic leukemia (ALL). JC virus is a potential candidate, offering new insights into pediatric leukemia etiology.
Area of Science:
- Pediatric Oncology
- Infectious Disease Epidemiology
- Viral Oncology
Background:
- Evidence suggests an infectious agent contributes to childhood acute lymphoblastic leukemia (ALL) in the 2-5 year age range.
- Existing models propose post-natal infection, with later infections having greater leukemogenic potential.
- An alternative hypothesis posits a prenatal infectious event as the critical factor for a subset of childhood ALL.
Purpose of the Study:
- To propose an alternative model for the etiology of a subset of childhood ALL.
- To identify characteristics of a potential prenatal infectious agent responsible for childhood ALL.
- To evaluate JC virus as a candidate agent based on proposed criteria.
Main Methods:
- Literature review and hypothesis generation.
- Characterization of hypothetical infectious agent properties.
- Assessment of JC virus against proposed criteria.
Main Results:
- Proposed a model where prenatal infection of the mother, transmitted to the fetus, increases ALL risk before age 5.
- Defined key characteristics for the causative agent: genomic instability induction, B-lymphocyte specificity, association with lower socioeconomic status, limited oncogenicity, mild maternal symptoms, and placental transfer without severe fetal abnormalities.
- Identified JC virus as a potential candidate meeting many of these criteria, particularly for hyperdiploid ALL.
Conclusions:
- Prenatal infection is a plausible etiology for a subset of childhood ALL.
- JC virus warrants further investigation as a potential causative agent in pediatric ALL.
- This hypothesis provides a new framework for understanding the origins of childhood leukemia.
Abstract:
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.