Page 270 - Haematologica Vol. 107 - September 2022

LETTER TO THE EDITOR
our detection rate of CMV proteins in the current study mirrors this maternal prevalence rather than the newborn. Proteins cross the placental barrier by active transport as well as passive diffusion, the latter at a rate equivalent to the concentration of the protein.15
Accepting the source of CMV proteins from the pregnant mother, the correlative structure of proteins assessed here implicate that CMV infection of the mother impacts immune development of the fetus and may be the source of cytokine alterations at birth that distinguish ALL cases from controls in this and prior studies.1,3,4,7 Significant cor- relations between maternal cytokines and neonatal CMV proteins (and neonatal cytokines) suggest direct or indi- rect manipulation of immune function, even in the ab- sence of primary CMV infection of the neonate. Most notable here is the higher level of CMV-IL-10 found in neo- nates who grew up to be cases compared to controls who remained healthy. This cytokine interacts directly with the human IL-10 receptor, but is only one of several CMV genes that manipulate the immune system. The presence of CMV-IL-10 protein as a risk factor for ALL requires more analysis to examine whether it is simply a marker of pri- mary CMV infection or is itself the factor that alters neo- natal immunity impacting risk of ALL, and therefore pinpoints maternal CMV activity as consequential to ALL risk in the offspring.
To conclude, our results suggest that CMV infection is re- sponsible at least in part for the neonatal cytokine pro- files that are associated with risk of childhood ALL. Our results should be considered preliminary as the findings will not meet the more stringent threshold for statistical significance with correction for multiple comparisons, hence the potential for false discovery. CMV is, however, the first specific target for ALL prevention and potentially treatment, and its role in the pathogenesis of childhood ALL and prevention deserves further examination.
Authors
Joseph L. Wiemels,1 Rong Wang,2 Mi Zhou,3 Helen Hansen,3 Rachel Gallant,1,4 Junghyun Jung,1 Nicholas Mancuso,1 Adam J. de Smith,1 Catherine Metayer,5 Scott C. Kogan3 and Xiaomei Ma2
1Center for Genetic Epidemiology, Norris Comprehensive Cancer Center, and Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA; 2Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT; 3School of Medicine; University of California San Francisco, San Francisco, CA; 4Children’s Hospital Los
Angeles, Los Angeles, CA and 5School of Public Health, University of California, Berkeley, Berkeley, CA, USA
Correspondence:
J.L. WIEMELS - wiemels@usc.edu
https://doi.org/10.3324/haematol.2022.280826
Received: February 8, 2022. Accepted: May 27, 2022. Prepublished: May 31, 2022.
©2022 Ferrata Storti Foundation Published under a CC BY-NC license
Disclosures
No conflicts of interest to disclose.
Contributions
JLW and XM designed the research with assistance from CM, obtained the funding, and wrote the manuscript; RW performed the statistical analysis; MZ designed laboratory assays and with HH performed the laboratory measurements; RG, JJ, NM, AJdS, and SCG assisted with analysis and interpretation. All authors reviewed and approved the manuscript.
Acknowledgments
The biospecimens used in this study were obtained from the California Biobank Program, (Screening Information System request number 600), in accordance with Section 6555(b), 17 CCR. The California Department of Public Health (CDPH) is not responsible for the results or conclusions drawn by the authors of this publication. This manuscript is solely the responsibility of the authors and the content does not necessarily represent the official views of the National Institutes of Health. Special thanks to Robin Cooley and Martin Kharrazi (CDPH).
Funding
Research reported in this publication was supported by the National Institutes Health under award numbers R01CA175737 (JLW and XM) and R01CA185058 (JLW and SCK).
Data-sharing statement
We are prohibited by California statutes from publicly sharing data that are derived from biospecimens obtained from the California Biobank. We welcome questions from other investigators or request for additional analyses that are pertinent to the data presented in this Letter, and potential data sharing when permitted by the California Health and Human Services Agency Committee for the Protection of Human Subjects.
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