Evidence shows that in most cases of acute lymphoblastic leukemia - the most common childhood cancer - the origins are prenatal. There is also a controversial suggestion that congenital infection could play a role. Now, a new study finds that children who develop the cancer are over three times more likely to have tested positive for the common herpes virus cytomegalovirus at birth.
Lead author Stephen Francis - assistant professor of Epidemiology at the University of Nevada and University of California, San Francisco - and colleagues report their findings in the journal Blood.
The cells do not develop in the same way as normal white blood cells, and they cannot fight infection very well. Also, as their numbers increase, there is less room for stem cells to make healthy white blood cells, red blood cells, and platelets. This increases the likelihood of infection, anemia, and easy bleeding.
Having had treatment for cancer and certain genetic conditions appears to affect the risk of developing childhood ALL, the signs of which include fever and bruising. ALL is the most common cancer in children; it typically develops between the ages of 2-6 years and usually worsens rapidly if not treated.
Although researchers have long suspected that infection plays a role in childhood ALL, the new study is the first to track it back to a specific virus.
Once a person is infected with CMV, the virus stays in the body for life, where it usually remains dormant. Most people experience no signs or symptoms of CMV infection.
However, the virus can flare up during pregnancy and transmit to the fetus, with serious consequences, such as birth defects and hearing loss in newborns. People with a weak immune system can also develop serious health problems from CMV infection.
CMV-positive at birth linked to higher odds of childhood ALL
For their study, Prof. Francis and colleagues first compared bone marrow infections in 127 children diagnosed with ALL, and in 38 children diagnosed with another type of leukemia - acute myeloid leukemia (AML).
- Estimates suggest that there will be 6,590 new cases of ALL in the United States in 2016
- Overall, about 6 out of every 10 cases occur in children
- The average person's lifetime risk of getting ALL is less than 1 in 750.
Using state-of-the-art methods, the researchers screened the samples for all known viruses and bacteria. They found genetic traces of CMV in abnormal white blood cells and intact virus particles in blood samples in the children with ALL, but rarely in those with AML.
Then, the researchers used an ultra-sensitive digital droplet screen to test for CMV in newborn blood samples of 268 children who went on to develop ALL. They also tested newborn blood samples from 270 healthy children.
They found that the children who went on to develop ALL were 3.71 times more likely to be CMV-positive at birth.
The odds were higher for Hispanic children who developed ALL - they were 5.9 times more likely to be CMV-positive at birth. The researchers suggest that this is an important finding because Hispanic people have the highest risk of developing ALL.
Prof. Francis says that their goal was to show that CMV infection occurred well before the onset of ALL.
He and his colleagues note that while it is still early days, they hope that the findings will spur more research to confirm their results. If they also find that CMV causes ALL, then these results may lead to the development of a vaccine for CMV and therefore prevent mother-to-child transmission.
"If it's truly that in-utero CMV is one of the initiating events in the development of childhood leukemia, then control of the virus has the potential to be a prevention target. That's the real take-home message."
Prof. Stephen Francis