Untargeted Adductomics of Newborn Dried Blood Spots Identifies Modifications to Human Serum Albumin Associated with Childhood Leukemia

Overview

Journal Leuk Res

Date 2019 Nov 25

PMID 31760269

Citations 15

Authors

Yukiko Yano

Courtney Schiffman

Hasmik Grigoryan

Josie Hayes

William Edmands

Lauren Petrick

Todd Whitehead

Catherine Metayer

Sandrine Dudoit

Stephen Rappaport

Affiliations

Soon will be listed here.

Abstract

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.

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References

Blom H, Smulders Y . Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. J Inherit Metab Dis. 2010; 34(1):75-81. PMC: 3026708. DOI: 10.1007/s10545-010-9177-4. View

Yamashita Y, Yuan J, Suetake I, Suzuki H, Ishikawa Y, Choi Y . Array-based genomic resequencing of human leukemia. Oncogene. 2010; 29(25):3723-31. DOI: 10.1038/onc.2010.117. View

Grimwade D, Ivey A, Huntly B . Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance. Blood. 2015; 127(1):29-41. PMC: 4705608. DOI: 10.1182/blood-2015-07-604496. View

Grigoryan H, Li H, Iavarone A, Williams E, Rappaport S . Cys34 adducts of reactive oxygen species in human serum albumin. Chem Res Toxicol. 2012; 25(8):1633-42. PMC: 4763613. DOI: 10.1021/tx300096a. View

Ehrlich M . DNA methylation in cancer: too much, but also too little. Oncogene. 2002; 21(35):5400-13. DOI: 10.1038/sj.onc.1205651. View

Petrick L, Schiffman C, Edmands W, Yano Y, Perttula K, Whitehead T . Metabolomics of neonatal blood spots reveal distinct phenotypes of pediatric acute lymphoblastic leukemia and potential effects of early-life nutrition. Cancer Lett. 2019; 452:71-78. PMC: 6499387. DOI: 10.1016/j.canlet.2019.03.007. View

Greaves M . A causal mechanism for childhood acute lymphoblastic leukaemia. Nat Rev Cancer. 2018; 18(8):471-484. PMC: 6986894. DOI: 10.1038/s41568-018-0015-6. View

Yano Y, Grigoryan H, Schiffman C, Edmands W, Petrick L, Hall K . Untargeted adductomics of Cys34 modifications to human serum albumin in newborn dried blood spots. Anal Bioanal Chem. 2019; 411(11):2351-2362. PMC: 6461474. DOI: 10.1007/s00216-019-01675-8. View

Schiffman C, Petrick L, Perttula K, Yano Y, Carlsson H, Whitehead T . Filtering procedures for untargeted LC-MS metabolomics data. BMC Bioinformatics. 2019; 20(1):334. PMC: 6570933. DOI: 10.1186/s12859-019-2871-9. View

10.

Lu S, Grigoryan H, Edmands W, Hu W, Iavarone A, Hubbard A . Profiling the Serum Albumin Cys34 Adductome of Solid Fuel Users in Xuanwei and Fuyuan, China. Environ Sci Technol. 2016; 51(1):46-57. PMC: 5567851. DOI: 10.1021/acs.est.6b03955. View

11.

Liu S, Grigoryan H, Edmands W, Dagnino S, Sinharay R, Cullinan P . Cys34 Adductomes Differ between Patients with Chronic Lung or Heart Disease and Healthy Controls in Central London. Environ Sci Technol. 2018; 52(4):2307-2313. DOI: 10.1021/acs.est.7b05554. View

12.

Pfeiffer C, Caudill S, Gunter E, Osterloh J, Sampson E . Biochemical indicators of B vitamin status in the US population after folic acid fortification: results from the National Health and Nutrition Examination Survey 1999-2000. Am J Clin Nutr. 2005; 82(2):442-50. DOI: 10.1093/ajcn.82.2.442. View

13.

Lightfoot T, Johnston W, Painter D, Simpson J, Roman E, Skibola C . Genetic variation in the folate metabolic pathway and risk of childhood leukemia. Blood. 2010; 115(19):3923-9. PMC: 2869556. DOI: 10.1182/blood-2009-10-249722. View

14.

Metayer C, Milne E, Dockerty J, Clavel J, Pombo-de-Oliveira M, Wesseling C . Maternal supplementation with folic acid and other vitamins and risk of leukemia in offspring: a Childhood Leukemia International Consortium study. Epidemiology. 2014; 25(6):811-22. PMC: 5903563. DOI: 10.1097/EDE.0000000000000141. View

15.

Corces-Zimmerman M, Hong W, Weissman I, Medeiros B, Majeti R . Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proc Natl Acad Sci U S A. 2014; 111(7):2548-53. PMC: 3932921. DOI: 10.1073/pnas.1324297111. View

16.

Pui C, Carroll W, Meshinchi S, Arceci R . Biology, risk stratification, and therapy of pediatric acute leukemias: an update. J Clin Oncol. 2011; 29(5):551-65. PMC: 3071256. DOI: 10.1200/JCO.2010.30.7405. View

17.

Battisti V, Maders L, Bagatini M, Santos K, Spanevello R, Maldonado P . Measurement of oxidative stress and antioxidant status in acute lymphoblastic leukemia patients. Clin Biochem. 2008; 41(7-8):511-8. DOI: 10.1016/j.clinbiochem.2008.01.027. View

18.

Wiemels J . Perspectives on the causes of childhood leukemia. Chem Biol Interact. 2012; 196(3):59-67. PMC: 3839796. DOI: 10.1016/j.cbi.2012.01.007. View

19.

Metayer C, Milne E, Clavel J, Infante-Rivard C, Petridou E, Taylor M . The Childhood Leukemia International Consortium. Cancer Epidemiol. 2013; 37(3):336-47. PMC: 3652629. DOI: 10.1016/j.canep.2012.12.011. View

20.

Rappaport S, Li H, Grigoryan H, Funk W, Williams E . Adductomics: characterizing exposures to reactive electrophiles. Toxicol Lett. 2011; 213(1):83-90. PMC: 4758449. DOI: 10.1016/j.toxlet.2011.04.002. View