Untargeted adductomics of newborn dried blood spots identifies modifications to human serum albumin associated with childhood leukemia.
Adolescent
Age of Onset
Case-Control Studies
Child
Child, Preschool
Chromatography, High Pressure Liquid
Dried Blood Spot Testing
/ methods
Female
Humans
Infant
Infant, Newborn
Leukemia
/ blood
Lipid Peroxidation
Male
Neonatal Screening
/ methods
Oxidative Stress
/ physiology
Protein Processing, Post-Translational
Proteomics
/ methods
Reactive Oxygen Species
/ analysis
Serum Albumin, Human
/ analysis
Adductomics
Childhood leukemia
Human serum albumin
In utero exposures
Newborn blood spots
Journal
Leukemia research
ISSN: 1873-5835
Titre abrégé: Leuk Res
Pays: England
ID NLM: 7706787
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
23
10
2019
revised:
04
11
2019
accepted:
05
11
2019
pubmed:
25
11
2019
medline:
15
7
2020
entrez:
25
11
2019
Statut:
ppublish
Résumé
The developing fetus is exposed to chemicals, which are metabolized to electrophiles that form adducts with nucleophilic Cys34 of human serum albumin (HSA). By measuring these adducts in neonatal blood spots (NBS), we obtain information regarding fetal exposures during the last month of gestation. To discover potential risk factors for childhood leukemia resulting from in utero exposures, we used untargeted adductomics to measure HSA-Cys34 adducts in 782 archived NBS, collected from incident cases of childhood acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) and matched population-based controls. Among a total of 28 Cys34 modifications that were measured, we found no differences in adduct abundances between childhood leukemia cases and controls overall. However, cases of T-cell ALL had higher abundances of adducts of reactive carbonyl species and a Cys34 disulfide of homocysteine was present at lower levels in AML cases. These results suggest that oxidative stress and lipid peroxidation may be etiologic factors of T-cell ALL, and alterations in one-carbon metabolism and epigenetic changes may be predictors of AML. Future replication of the results with larger sample sizes is necessary.
Identifiants
pubmed: 31760269
pii: S0145-2126(19)30713-1
doi: 10.1016/j.leukres.2019.106268
pmc: PMC6937378
mid: NIHMS1544419
pii:
doi:
Substances chimiques
Reactive Oxygen Species
0
Serum Albumin, Human
ZIF514RVZR
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
106268Subventions
Organisme : NIEHS NIH HHS
ID : R24 ES028524
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES004705
Pays : United States
Organisme : NIEHS NIH HHS
ID : P50 ES018172
Pays : United States
Organisme : NIEHS NIH HHS
ID : P01 ES018172
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES009137
Pays : United States
Organisme : EPA
ID : R836159
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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