Exploring The Origins Of Childhood Leukaemia

29 Mar 2020

Child with Cancer

Researchers analyse archived newborn blood spots to look for exposures in the womb that may affect the risk of developing the most common childhood cancer.

Recent evidence suggests that childhood leukaemia involves at least two events – the first occurring when the baby is developing in the womb, with a second following after their birth. Although the precise factors that contribute to these events are not fully understood, the rising incidence of childhood leukaemia over time, particularly in affluent countries, suggests that environmental and lifestyle factors are involved.

Both the developing fetus and child are exposed to a multitude of potentially harmful chemicals – such as those generated from intrinsic metabolic processes or from exogenous sources including infections, diet or parental smoking.

Although many of these chemicals are stable molecules that can be measured with techniques such as metabolomics or proteomics, others are metabolised into electrophilic compounds that can alter physiological processes in early life but can’t be measured in the body. This makes it challenging for researchers to investigate their potential impact on the risk of developing a disease later in life.

A Proxy Marker In Newborn Blood Spots

The Cys34 residue of the most abundant blood protein, human serum albumin (HSA), is a powerful scavenger of electrophilic compounds. As its turnover in the body is 28 days, measuring the modifications (adducts) of this amino acid in archived newborn blood spots offers an indirect way to capture fetal exposures during the last month of pregnancy.

In a new study, published in Leukemia Research, a team of researchers analysed these Cys34 adducts in the HSA protein in archived newborn blood spots as a way obtain new information about exposures in the womb and investigate how these may impact on the risk of childhood leukaemia.1

The team used an adapted untargeted adductomics method based on nanoflow liquid chromatography-high resolution mass spectrometry (nLC-HRMS) to characterise Cys34 adducts in the archived newborn blood spots. They used ultrapure water from an ELGA PURELAB® laboratory water purification system to minimise the risk of introducing contaminants that may affect the results of this sensitive analytical technique.

Comparing Abundances In Cases And Controls

The researchers analysed 782 archived newborn blood spots collected from participants of the California Childhood Leukaemia Study (CCLS) – including 338 children with acute lymphoblastic leukaemia (ALL), 45 with acute myeloid leukaemia (AML) and matched healthy controls.

While they identified no clear associations between adduct abundance with either childhood leukaemia or ALL overall, they did identify differences between samples from children with subtypes of the disease and healthy controls – albeit in small sample sizes.

Children with T-cell ALL had higher abundances of adducts of reactive carbonyl species. And interestingly, there was a 44% decrease in abundances of a homocysteine adduct in AML cases.

Preventing Childhood Leukaemia

Although the results shed light on potential exposures involved in the development of certain subtypes of ALL before birth, larger studies are now needed to confirm these findings and further explore their implications.

As there are very few known lifestyle-related or environmental causes of childhood leukaemias, identifying modifiable risk factors could lead to new ways to help reduce the risk of the disease.

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Reference:

Yano, Y. et al. Untargeted Adductomics of Newborn Dried Blood Spots Identifies Modifications to Human Serum Albumin Associated with Childhood Leukaemia. Leukemia Research 2019; S0145-2126(19)30713-1.

Dr Alison Halliday
After completing an undergraduate degree in Biochemistry & Genetics at Sheffield University, Alison was awarded a PhD in Human Molecular Genetics at the University of Newcastle. She carried out five years as a Senior Postdoctoral Research Fellow at UCL, investigating the genes involved in childhood obesity syndrome. Moving into science communications, she spent ten years at Cancer Research UK engaging the public about the charity’s work. She now specialises in writing about research across the life sciences, medicine and health.