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Children With B-Cell Precursor ALL Have Dysregulated Immune Function

David Bai, PharmD
Abnormal concentrations of inflammatory markers detected in children with B-cell precursor acute lymphoblastic leukemia (ALL) support the theory that children with ALL are born with dysregulated immune function. 
Abnormal concentrations of inflammatory markers detected in children with B-cell precursor acute lymphoblastic leukemia (ALL) support the theory that children with ALL are born with dysregulated immune function. 

 
The etiology of childhood ALL has been of interest for some time, but it has been inadequately analyzed. In the past, there was an assumption, the delayed infection hypothesis, that held that a lack of infections in early childhood caused abnormal immune responses later, leading to the transformation of preleukemic cells to leukemia.



However, this hypothesis has been challenged multiple times based on inconsistencies from epidemiologic studies. At present, there is a newer theory proposing that children with ALL are born with abnormal immune function, resulting in numerous infections during the first year of life. A previous study by Chang et al showed differences in inflammatory markers between children with ALL and children serving as controls. Recently, Signe Holst Søegaard, MSc, PhD fellow in the Department of Epidemiology Research at Statens Serum Institute in Copenhagen, Denmark, and colleagues sought to strengthen the connection between neonatal inflammatory markers and childhood ALL.

In the study, Søegaard and colleagues matched 178 children with B-cell precursor ALL with 178 controls. Patients in both groups had dried blood spot samples collected to analyze 9 different inflammatory markers: sIL6RαTGFβ1MCP-1CRP, IL6, IL8, IL12, IL17, andIL18

Among the 9 inflammatory markers, 8 of them had statistically significant differences between the 2 groups. Neonatal concentrations of sIL6RαIL8TGFβ1MCP-1, and CRPwere all significantly lower in the B-cell precursor ALL group compared with the control group. In contrast, IL6IL17, and IL18were all significantly higher in the B-cell precursor ALL group compared with the control group. 

When observing for any baseline characteristics that affected inflammatory marker concentrations, investigators found that birth order, gestational age, and sex were linked with significant changes. Higher birth orders led to a significantly higher IL18and a significantly lower CRPconcentration. Increasing gestational age was associated with a 5% lower sIL6Rαconcentration, and a 4% lower TGFβ1concentration. Gender discrepancies also revealed boys to have 9% lower sIL6Rαconcentration, 8% lower IL8concentration, and 22% higher CRPconcentration than girls.

This study and the previous study by Chang et al support the hypothesis of an abnormal immune function in children with ALL. Because the dysfunction in immune function is detectable at birth, there is opportunity “for the prevention of childhood ALL through early immune modulation,” Søegaard saidin a statement. Additional inflammatory markers and risk factors of ALL should be investigated in future studies.

Reference

Søegaard S, Rostgaard K, Skogstrand K, Wiemels JL, Schmiegelow K, Hjalgrim H. Neonatal inflammatory markers are associated with childhood B-cell precursor acute lymphoblastic leukemia. Cancer Res. 2018;78(18):5458-5463. doi: 10.1158/0008-5472.CAN-18-0831.

 
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