CTA: Even if CMV turns out to be a causal factor in leukemogenesis, would other factors also be involved?
Dr Wiemels: There are likely to be multiple factors that cause childhood leukemia, and CMV infection before birth may only account for a portion of cases. Whether CMV plays a role in 10% or 50% we cannot say now, although we can be fairly certain that there are additional pathways to reach leukemia that do not involve CMV. But we believe that our data warrant consideration of additional efforts to reduce CMV infection or reactivation during pregnancy, which is already advisable for pregnant women, in order to prevent neurological abnormalities and hearing loss which can be a consequence of a fulminant CMV infection during pregnancy. The New York Times recently reported on these concerns.3
Even in cases with the presence of CMV, our data does not suggest that CMV by itself causes the leukemia. There are likely to be other factors – additional infections, chemical exposures, and an element of chance, which play a role. But if CMV was an obligate precursor to the leukemia, then the data suggest a possible role for CMV vaccination for leukemia prevention or control.
CTA: What are the clinical and prevention implications, should these findings be confirmed in subsequent studies? Might antivirals or targeted vaccination programs reduce the risk of childhood leukemia?
Dr Wiemels: If we take the brain cancer story, antivirals may be able to be tried against leukemia.4 I think the best public health prevention measures will be to try to prevent CMV infection during pregnancy, as in the New York Times article particularly, since it helps prevent additional more frequent health outcomes and does not need pharmacological intervention. If CMV becomes part of a state screening program (like they are trying out in Minnesota) then we can consider prophylactic vaccination for children to prevent CMV related damage that happens after birth (including, possibly, leukemia).
CTA: Have similar studies been planned or undertaken, using these same sequencing tools, to examine adult leukemias, or pediatric brain cancers?
Dr Wiemels: Brain cancers have been studied since 2002, but remain controversial.5 Many studies have detected CMV, but there is little DNA and some proteins, and additional investigators have had a hard time detecting these in brain tumors. There is an example of a CMV related vaccine that seems effective against brain cancer.6 This is a very active research field with great hopes for brain cancers which have a much worse prognosis than leukemias.
There are no other studies of CMV involvement in leukemia published, but we are planning many more studies into CMV in childhood leukemia and also brain cancer. To some extent the cancer research community has been obsessed with inborn and tumor genetics over the last 2 decades, due to the discovery power of technology in these areas, but our work may help rekindle an interest in infectious agents and cancer.
- Francis SS, Wallace AD, Wendt GA, et al. In utero cytomegalovirus infection and development of childhood acute lymphoblastic leukemia. Blood. In press.
- Bogdanovic G, Pou C, Barrientos-Somarribas M, et al. Virome characterization from Guthrie cards in children who later developed acute lymphoblastic leukaemia. Br J Cancer. 2016;115(8):1008-14. doi: 10.1038/bjc.2016.261
- Saint Louis C. CMV is a greater threat to infants than Zika, but far less often discussed. The New York Times website. http://www.nytimes.com/2016/10/25/health/cmv-cytomegalovirus-pregnancy.html. Updated October 24, 2016. Accessed November 2016.
- Söderberg-Nauclér C, Rahbar A, Stragliotto G. Survival in patients with glioblastoma receiving valganciclovir. New Engl J Med. 2013;369(10):985-6.
- Cobbs CS. Evolving evidence implicates cytomegalovirus as a promoter of malignant glioma pathogenesis. Herpesviridae. 2011;2(1):10. doi: 10.1186/2042-4280-2-10.
- Mitchell DA, Batich KA, Gunn MD, et al. Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature. 2015;519:366-9. doi: 10.1038/nature14320