In utero cytomegalovirus infection and development of childhood acute lymphoblastic leukemia
Maternal infections during pregnancy are suspected to play a role in the development of childhood ALL through generation of genomic instability. So far, scientific evidence for this theory is controversial. This article addresses the question whether maternal viral infections are associated with ALL. The retrospective case-control study was done as part of the California Childhood Leukemia Study (CCLS).
The study was set up in a two-step approach by (1) screening of the diagnostic bone marrow of 127 ALL and 38 AML patients for presence of viral particles by using a comprehensive next-generation sequencing (NGS)-based viral and bacterial metagenomics assay; and then after identification of candidates: (2) targeted viral DNA sequencing by digital droplet PCR of the candidate pathogens in newborn dried blood spot DNA of 268 ALL cases and 270 healthy controls.
Neonatal cytomegalovirus (CMV) was identified as a candidate in the first part of the study as it was significantly more prevalent in the bone marrow of patients with ALL compared to AML (OR 18, p=0.03). In the second phase, CMV was detected in neonatal dry blood spots of cases and controls and was associated with an increased risk of ALL (OR 3.71, CI 1.56-7.92). In a subgroup analysis, this association was only significant in Hispanics and not in non-Hispanic whites.
This study used two highly sensitive assays (NGS) to detect CMV particles in the bone marrow of ALL and AML patients and by another highly sensitive assay after birth in ALL cases versus healthy controls. The significance of using these techniques clinically for viral detection is unclear. Interesting, the association was not found in a subgroup analysis of non-Hispanic whites which raises questions on the generalizability of the results.