Considerations on a possible viral etiology for B-precursor acute lymphoblastic leukemia of childhood.
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.
Smith
M
M
Pediatric Section, Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland 20892, USA.
D000328:Adult; D002648:Child; D005260:Female; D016678:Genome; D006801:Humans; D007577:JC Virus / Q000302:isolation & purification* / Q000502:physiology; D027601:Polyomavirus Infections / Q000150:complications* / Q000453:epidemiology; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000821:virology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000821:virology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D014412:Tumor Virus Infections / Q000150:complications* / Q000453:epidemiology
D016159:Tumor Suppressor Protein p53