For years, scientists have noticed an interesting trend of childhood cancer. Those who went to daycare early in life were less likely to develop later a most common childhood cancers: acute lymphoblastic leukemia (ALL). Now, a 7-year study seems to have deciphered the molecular mechanism of ALL training. The work may explain why early exposure to infections in places like day care appears to protect against the disease and why vaccines unrelated help protect against this cancer.
For Mel Greaves, a cell biologist cancer at the University of London Cancer Research Institute, the discovery provides an explanation for the hypothesis that it promotes a long time: that when infants in modern societies are immune to common infections, their immune systems are more likely to overreact in subsequent infections, paving the way for ALL. "I see it as the missing link," he said of the new research.
Most childhood involves all malfunction of B cells, scouts immune patrolling in the bloodstream in search intruders such as viruses and bacteria; they make antibodies that help fight infections, but with leukemia, the immune system goes haywire, imperfect churning B cells, immature at a prodigious rate and crowding out healthy blood cells [
normal B cells are a marvel of adaptation. As they age, they reprogram their own DNA, allowing the immune system to produce millions of different B cells programmed to recognize the wide range of potential infections. the DNA shuffling based on a sequence of enzymes. first, the proteins known under the name RAGs cutting and pasting whole chunks of DNA. After that, another enzyme, AID, will work 'fine tuning' DNA nucleotides by changing simple.
But Greaves and his colleagues suspected that process could go wrong, introducing mutations that create faulty B cells that might cause leukemia. In a series of experiments, they found evidence that much of the problem lies in a break in the ordered sequence of editing genes during infection. Rather than RAGs do their business, then step aside for IDA, IDA began at the same time, potentially increasing the risk of gene-editing errors.
These mouthwatering results came to a head in an experiment on mice with a genetic defect linked to childhood ALL. The condition in which two genes associated with blood formation are fused together, is found in the umbilical cord blood of 1% of all newborns. But most children with her are never going to develop ALL in itself. The researchers wondered if unregulated mutations triggered by repeated infection later in childhood could make the difference, the trigger leukemia.
The scientists made mouse B cells with this genetic defect. Some products both RAG and using enzymes and other cells made only one of two. They then simulated repeated illnesses by subjecting the rodents to five cycles of exposure to a molecule that acts as an antigen of a substance eliciting an immune response. In this case, it mimics a bacterial infection. At the same time, they removed the protein which normally acts as a traffic cop, coordination when enzymes are involved.
When the cells were injected into mice, 14 mice that B cells obtained with both enzymes quickly got leukemia and died, reports the online team today Nature Immunology . The mice with B cells producing a single enzyme were even five months later without disease.
"This is a smoking gun," says Markus Müschen, lead author of the paper and a cancer researcher at the University of California, San Francisco (UCSF). "Now we know that this is AID and RAG. And now we know it can be triggered by bacterial antigens. "
The results, Müschen said, referring to why several studies have found a link between a decrease in all cases and the vaccine Haemophilus influenzae type B (Hib) , a bacterial infection that most often affects young children. the vaccine could trigger a mild immune response in infants that mimics normal sniffling children learn in child care, while preventing more intense infections that could lead to dysfunction immune system, he said.
the document could become ammunition political struggle on the vaccination of children, if vaccines proponents argue that highlights the benefits of vaccines. the California State Senate last week adopted a bill which eliminates the exemption that allows parents to opt out of vaccination for their children according to personal convictions. It is now before the State Assembly. The move comes on the heels of a measles epidemic centered in Disneyland, that those responsible for public health were linked to lower immunization rates.
Joseph Wiemels, a researcher of childhood leukemia at UCSF who was not involved in the research, praised the work as important evidence of how infections may play a role in such leukemia. It could also help explain the apparently contradictory results that even so early day care reduces all risks, this same risk is higher in children with more doctor visits. There may be mild infections early in life, such as those that often circulate in child care, help build the immune system. More serious infections that are worth a visit to the doctor, however, could trigger a damaging immune "storm," he said.
But Wiemels warns against hasty conclusions. The study offers a plausible explanation why a Hib vaccine as might help. But he notes that scientists are not actually test the impact of the vaccine or a previous illness. "They do not take these mice and vaccinate them or having their immune system, and then hit them."
Greaves said the most striking reduction in ALL is for children who spend time at the beginning of day care. Although the Hib vaccine appears to have an advantage, it is not perfect. And there is less evidence that other vaccines help, he said. "If it really worked as well as this, we would not have leukemia."
A big unanswered question is whether some infections are more likely to trigger the mutations leading to ALL. Greaves said although there is little evidence that a single virus is still the case, he is working on a document that highlights a virus in a cluster of leukemia cases. Meanwhile, Wiemels prepares the results of a study that points to a link between a specific viral infection in pregnancy and childhood leukemia.
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