Nav: Home

Children who develop ALL may have dysregulated immune function at birth

September 14, 2018

Bottom Line: Neonatal concentrations of eight detectable inflammatory markers were significantly different in children later diagnosed with B-cell precursor acute lymphoblastic leukemia (ALL) compared with controls.

Journal in Which the Study was Published: Cancer Research, a journal of the American Association for Cancer Research.

Author: Signe Holst Søegaard, MSc, PhD fellow in the Department of Epidemiology Research at Statens Serum Institut in Copenhagen, Denmark

Background: Prior research indicates that ALL could develop in children because of an overreaction to infections in childhood, Søegaard explained. This may hold promise for the prevention of childhood ALL through early immune modulation, she added.

How the Study Was Conducted: Søegaard and colleagues used data from Denmark's Neonatal Screening Biobank and nationwide registers to assess baseline characteristics of the immune system of children born in Denmark from 1995 to 2008, who at ages 1-9 years were diagnosed with B-cell precursor ALL, the most common ALL subtype in children. They measured the concentrations of inflammatory markers, including cytokines and acute inflammatory proteins, on neonatal dried blood spots from 178 childhood ALL patients and 178 matched leukemia-free controls.

Inflammatory markers included interleukin (IL)-6, its soluble receptor sIL-6Rα, IL-8, IL-10, IL-12, IL-17, IL-18, transforming growth factor (TGF)-β1, monocyte chemotactic protein (MCP)-1, and C-reactive protein (CRP). "These markers were chosen to provide a broad picture of the neonatal immune response," Søegaard said.

Results: Children who later developed B-cell precursor ALL had statistically significantly different neonatal concentrations of eight of the nine analyzed inflammatory markers, compared with controls. IL-10 concentrations were too low for accurate measurement. Neonatal concentrations of sIL-6Rα, IL-8, TGF-β1, MCP-1, and CRP were statistically significantly lower, while concentrations of IL-6, IL-17, and IL-18 were statistically significantly higher among B-cell precursor ALL patients, compared with controls.

"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," Søegaard noted. "These findings raise the interesting possibility that the effects of some known ALL risk factors partly act through prenatal programming of immune function.

Author's Comments: "Our findings suggest that children who develop ALL are immunologically disparate already at birth," said Søegaard. "This may link to other observations suggesting that children who develop ALL respond differently to infections in early childhood, potentially promoting subsequent genetic events required for transformation to ALL, or speculations that they are unable to eliminate preleukemic cells.

"Importantly, our study does not inform about the nature of the associations observed, i.e., whether they are causal or consequential. Accordingly, further studies are needed both to confirm the findings and to identify the underlying mechanisms," she emphasized.

"Our findings underline the role the child's baseline immune characteristics may play in the development of ALL. However, we cannot yet use our research results to predict who will develop childhood ALL. In future studies, we will further characterize the relation between immune constitution at birth and risk of childhood ALL with the ultimate goal of developing preventive strategies targeting predisposed children," Søegaard said.

Study Limitations: Limitations of the study include the small number of studied inflammatory markers and the limited sample size, which made it impossible to detect potential differences in the association with inflammatory markers between subtypes of B-cell precursor ALL, Søegaard said.
-end-
Funding & Disclosures: The study was conducted in collaboration with researchers at Statens Serum Institut in Copenhagen, University Hospital Rigshospitalet, Copenhagen, and University of Southern California, Los Angeles. The research was sponsored by the Dagmar Marshall Foundation, the A.P. Møller Foundation, the Danish Childhood Cancer Foundation, the Arvid Nilsson Foundation, and the Danish Cancer Research Foundation. Søegaard declares no conflict of interest.

American Association for Cancer Research

Related Children Articles:

Do children inherently want to help others?
A new special section of the journal Child Development includes a collection of ten empirical articles and one theoretical article focusing on the predictors, outcomes, and mechanisms related to children's motivations for prosocial actions, such as helping and sharing.
Children need conventional CPR; black and Hispanic children more likely to get Hands-Only
While compressions-only or Hands-Only CPR is as good as conventional CPR for adults, children benefit more from the conventional approach that includes rescue breaths.
Cohen Children's Medical Center study: Children on autism spectrum more likely to wander, disappear
A new study by researchers at Cohen Children's Medical Center of New York suggests that more than one-quarter million school-age children with autism spectrum disorder or other developmental disorders wander away from adult supervision each year.
The importance of children at play
Research highlights positive strengths in developmental learning for Latino children in low-income households based on their interactive play skills.
Racial disparities in pain children of children with appendicitis in EDs
Black children were less likely to receive any pain medication for moderate pain and less likely to receive opioids for severe pain than white children in a study of racial disparities in the pain management of children with appendicitis in emergency departments, according to an article published online by JAMA Pediatrics.
More Children News and Children Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Teaching For Better Humans
More than test scores or good grades — what do kids need to prepare them for the future? This hour, guest host Manoush Zomorodi and TED speakers explore how to help children grow into better humans, in and out of the classroom. Guests include educators Olympia Della Flora and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#535 Superior
Apologies for the delay getting this week's episode out! A technical glitch slowed us down, but all is once again well. This week, we look at the often troubling intertwining of science and race: its long history, its ability to persist even during periods of disrepute, and the current forms it takes as it resurfaces, leveraging the internet and nationalism to buoy itself. We speak with Angela Saini, independent journalist and author of the new book "Superior: The Return of Race Science", about where race science went and how it's coming back.