Children with Acute Lymphoblastic Leukemia May Be Immunologically Disparate at Birth

Investigators in Denmark have found new evidence suggesting that children who develop acute lymphoblastic leukemia may be predisposed from birth, and their immune responses to early childhood infections may offer clues to how the disease develops.

Childhood acute lymphoblastic leukemia (ALL) is a cancer of the blood and bone marrow originating in the T and B lymphoblasts in the bone marrow. In children with ALL, the bone marrow makes too many immature lymphocytes, and the immune system weakens. With a decrease in healthy red blood cells, white blood cells, and platelets, children can experience infections and anemia and may bleed easily. According to the National Cancer Institute, rates of childhood ALL have been on the rise along with other childhood cancers since 1975. It is the most commonly diagnosed cancer in children, making up about 25% of all cancer diagnoses in children under the age of 15 years.

With remission rates of about 98% and a 90% survival rate at 5 years, children with ALL today benefit from advances in treatment. Many symptoms of ALL are similar to other conditions and can include aches in the arms and legs, unexplained bruising, enlarged lymph nodes, unexplained fever, tiredness, unexplained weight loss, and prolonged bleeding from minor injuries. Risk factors for children developing ALL include prenatal exposure to x-rays, post-natal exposure to high levels of radiation, chemotherapy treatment, inherited genetic variants, and genetic conditions including Down syndrome.

In a new study published in the journal Cancer Research, a research team led by scientists at the Statens Serum Institut in Copenhagen, Denmark, explored the hypothesis that children with ALL are born with a dysregulated immune function that together with postnatal environmental exposures causes the development of the disease in childhood. Previous studies had indicated that children could develop ALL due to an overreaction to childhood infections.

To understand the baseline characteristics of the immune systems of children diagnosed B-cell precursor ALL—the most common subtype of the disease in children ages 1 to 9 years—the research team used data collected through Denmark's Neonatal Screening Biobank and nationwide registers from 1995 to 2008. Using 178 blood samples each from childhood ALL patients and a control group of children without leukemia, the investigators measured the concentrations of 9 inflammatory markers such as interleukin (IL)-6, cytokines, and acute inflammatory proteins, which the study authors say were chosen to provide a broad picture of the neonatal immune response.

Compared with controls, the children who went on to develop B-cell precursor ALL had statistically significant differences in the neonatal concentrations of 8 of the 9 inflammatory markers. "We also demonstrated that several previously shown ALL risk factors, namely birth order, gestational age, and sex were associated with the neonatal concentrations of inflammatory markers," study author Signe Holst Søegaard, MSc, PhD, said in a recent statement from the American Association for Cancer Research. "These findings raise the interesting possibility that the effects of some known ALL risk factors partly act through prenatal programming of immune function.”

The findings, say the authors, add to previous indications that children with ALL may respond differently to infections during early childhood and may one day help investigators discover a way to prevent childhood ALL through early immune modulation.

In an interview with Rare Disease Report^®, Dr. Søegaard says other studies are needed to confirm the paper’s findings and to identify the underlying mechanisms. “Importantly, more research is needed, to clarify whether predisposed children with an aberrant immune system react abnormally to infections in childhood leading to ALL, or whether our observation reflects an immunological process that has already started,” he said.