Does Cytomegalovirus Play a Role in Pediatric Lymphoblastic Leukemogenesis?
Menée sur la période 1987-2014 à l'aide d'échantillons sanguins prélevés sur 4 756 témoins et 1 189 patients pédiatriques atteints d'une leucémie aiguë lymphoblastique (âge : 0-14 ans ; 57,6 % de garçons), cette étude analyse l'association entre une infection par le cytomégalovirus congénital et le risque de leucémie aiguë lymphoblastique
Acute lymphoblastic leukemia (ALL) is the most common cancer affecting children, and incidence rates have increased 2-fold over the past 70 years. Epidemiologists have long investigated patterns of infectious exposure and response in early life as causal factors, but no specific infectious agent was discovered until recently when cytomegalovirus (CMV) was found within childhood ALL blasts at diagnosis. Moreover, evaluation of neonatal blood spot–derived DNA in California patients revealed the presence of CMV at birth at a 3 to 5 fold higher frequency in children who contracted ALL later in childhood when compared with children that remained cancer-free. Geris et al attempted to reproduce this neonatal observation using samples from the Michigan State blood spot repository. Although CMV sequences were not found to be more frequent among ALL cases compared with healthy controls, Geris et al were able to show a higher prevalence and quantity of CMV in newborns who later developed ALL with high hyperdiploidy (HeH), an ALL subtype characterized by the presence of 51 to 68 chromosomes in the tumor and known to have a prenatal origin. Although the original neonatal results (Francis et al) were not replicated overall, the data are compatible with a recent observation that the frequency of CMV in ALL blasts at diagnosis is enhanced specifically in the HeH subtype when compared with other subtypes. Additional supportive clinical evidence for the CMV-ALL association was provided from Swedish registries where CMV infection diagnosed during pregnancy in the mother of children who contracted hematologic malignant neoplasms, or at birth in the newborn, was observed at a more than 10-fold higher frequency when compared with the remainder of the age-matched population. In sum, the evidence supporting an association between CMV and ALL is tantalizing and mounting rapidly, but much additional research attention is required to mechanistically describe pathways by which CMV may influence leukemia before the virus could be considered a potential target for prevention or clinical management of ALL.
JAMA Network Open , éditorial en libre accès, 2022