2023
Gene-Environment Analyses Reveal Novel Genetic Candidates with Prenatal Tobacco Exposure in Relation to Risk for Childhood Acute Lymphoblastic Leukemia.
Zhong C, Li S, Arroyo K, Morimoto L, de Smith A, Metayer C, Ma X, Kogan S, Gauderman W, Wiemels J. Gene-Environment Analyses Reveal Novel Genetic Candidates with Prenatal Tobacco Exposure in Relation to Risk for Childhood Acute Lymphoblastic Leukemia. Cancer Epidemiology Biomarkers & Prevention 2023, 32: 1707-1715. PMID: 37773025, DOI: 10.1158/1055-9965.epi-23-0258.Peer-Reviewed Original ResearchConceptsMaternal tobacco exposureAcute lymphoblastic leukemiaChildhood acute lymphoblastic leukemiaTobacco exposureLymphoblastic leukemiaLarge population-based studyPopulation-based studyEffects of tobaccoPrenatal tobacco exposureAryl hydrocarbon receptor repressor geneMode of deliverySelf-reported smokingIndividual-level risk factorsGenetic variantsPolygenetic risk scoresYear of birthAHRR hypomethylationSubsequent childhoodMaternal exposureGestational ageRisk factorsTobacco smokeRisk scoreBiological markersBlood spots
2022
Investigating DNA methylation as a mediator of genetic risk in childhood acute lymphoblastic leukemia
Xu K, Li S, Pandey P, Kang AY, Morimoto LM, Mancuso N, Ma X, Metayer C, Wiemels JL, de Smith AJ. Investigating DNA methylation as a mediator of genetic risk in childhood acute lymphoblastic leukemia. Human Molecular Genetics 2022, 31: 3741-3756. PMID: 35717575, PMCID: PMC9616572, DOI: 10.1093/hmg/ddac137.Peer-Reviewed Original ResearchMeSH KeywordsDNA MethylationGenome-Wide Association StudyHumansPolymorphism, Single NucleotidePrecursor Cell Lymphoblastic Leukemia-LymphomaTranscription FactorsConceptsEpigenome-wide association studiesSingle nucleotide polymorphismsGenetic risk lociDNA methylationRisk single nucleotide polymorphismsRisk lociAssociation studiesHeritable genetic variationGenome-wide association studiesMost single nucleotide polymorphismsDNA methylation differencesNon-European populationsEpigenetic mechanismsGenetic variationMethylation differencesSignificant DMPsPromoter regionFunctional pathwaysCpG positionsAssociation analysisFunctional roleMethylationNucleotide polymorphismsLociBlood DNA
2019
Inherited genetic susceptibility to acute lymphoblastic leukemia in Down syndrome
Brown AL, de Smith AJ, Gant VU, Yang W, Scheurer ME, Walsh KM, Chernus JM, Kallsen NA, Peyton SA, Davies GE, Ehli EA, Winick N, Heerema NA, Carroll AJ, Borowitz MJ, Wood BL, Carroll WL, Raetz EA, Feingold E, Devidas M, Barcellos LF, Hansen HM, Morimoto L, Kang AY, Smirnov I, Healy J, Laverdière C, Sinnett D, Taub JW, Birch JM, Thompson P, Spector LG, Pombo-de-Oliveira MS, DeWan AT, Mullighan CG, Hunger SP, Pui CH, Loh ML, Zwick ME, Metayer C, Ma X, Mueller BA, Sherman SL, Wiemels JL, Relling MV, Yang JJ, Lupo PJ, Rabin KR. Inherited genetic susceptibility to acute lymphoblastic leukemia in Down syndrome. Blood 2019, 134: 1227-1237. PMID: 31350265, PMCID: PMC6788009, DOI: 10.1182/blood.2018890764.Peer-Reviewed Original ResearchMeSH KeywordsChildCyclin-Dependent Kinase Inhibitor p16DNA-Binding ProteinsDown SyndromeGATA3 Transcription FactorGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansIkaros Transcription FactorPolymorphism, Single NucleotidePrecursor Cell Lymphoblastic Leukemia-LymphomaTranscription FactorsConceptsFirst genome-wide association studySusceptibility lociGenome-wide association studiesGenome-wide significanceFurther biological insightsGenetic variationEnhancer activityRisk lociBiological insightsLymphoblastoid cell linesAssociation studiesDifferential protein bindingFunctional significanceLociRisk allele frequenciesCell linesAllele frequenciesHigh penetranceRisk allelesProtein bindingCDKN2AGenetic susceptibilityHigher proliferationPenetranceAllele associations
2014
PTPRG inhibition by DNA methylation and cooperation with RAS gene activation in childhood acute lymphoblastic leukemia
Xiao J, Lee S, Xiao Y, Ma X, Houseman EA, Hsu L, Roy R, Wrensch M, de Smith A, Chokkalingam A, Buffler P, Wiencke JK, Wiemels JL. PTPRG inhibition by DNA methylation and cooperation with RAS gene activation in childhood acute lymphoblastic leukemia. International Journal Of Cancer 2014, 135: 1101-1109. PMID: 24496747, PMCID: PMC4776754, DOI: 10.1002/ijc.28759.Peer-Reviewed Original ResearchMeSH KeywordsCell Transformation, NeoplasticChildChild, PreschoolDNA MethylationDNA-Binding ProteinsEnzyme ActivationEpigenesis, GeneticExtracellular Signal-Regulated MAP KinasesGene Expression Regulation, LeukemicHEK293 CellsHumansMutationPhosphorylationPrecursor Cell Lymphoblastic Leukemia-LymphomaPromoter Regions, GeneticRas ProteinsReceptor-Like Protein Tyrosine Phosphatases, Class 5Transcription FactorsTranscriptional ActivationConceptsDNA methylationPTPRG expressionDNA methylation profilesDNA methylation statusDephosphorylation of ERKMember genesEpigenetic mechanismsGene activationMutant RASRAS gene activationMethylation profilesGene expressionPtprg geneMethylation statusCell growthAdditional roleMethylationPotential therapeutic targetCell linesGenetic characteristicsGenesLeukemia phenotypeTherapeutic targetMutationsExpression
2012
A global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network
Lee ST, Xiao Y, Muench MO, Xiao J, Fomin ME, Wiencke JK, Zheng S, Dou X, de Smith A, Chokkalingam A, Buffler P, Ma X, Wiemels JL. A global DNA methylation and gene expression analysis of early human B-cell development reveals a demethylation signature and transcription factor network. Nucleic Acids Research 2012, 40: 11339-11351. PMID: 23074194, PMCID: PMC3526268, DOI: 10.1093/nar/gks957.Peer-Reviewed Original ResearchConceptsB cell developmentDNA methylationMultipotent progenitorsDemethylation eventsEpigenetic changesGene body DNA methylationEarly B cell developmentTranscription factor networkTranscription factor sitesDNA methylation changesHuman B cell developmentB cell-related diseasesFeatures of promotersGene expression analysisGlobal DNA methylationTF occupancyGene bodiesPre-B-cell leukemiaFactor networkCpG islandsMethylation changesFactor sitesExpression analysisFetal bone marrowExpression arrays
2002
In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia
Wiemels JL, Xiao Z, Buffler PA, Maia AT, Ma X, Dicks BM, Smith MT, Zhang L, Feusner J, Wiencke J, Pritchard-Jones K, Kempski H, Greaves M. In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia. Blood 2002, 99: 3801-3805. PMID: 11986239, DOI: 10.1182/blood.v99.10.3801.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseChildChild, PreschoolChromosomes, Human, Pair 21Chromosomes, Human, Pair 8Core Binding Factor Alpha 2 SubunitDNA, NeoplasmHumansInfant, NewbornLeukemia, MyeloidOncogene Proteins, FusionRemission InductionRUNX1 Translocation Partner 1 ProteinTranscription FactorsTranslocation, GeneticConceptsChildhood acute myeloid leukemiaAcute myeloid leukemiaPrenatal originAML1–ETO translocationsMyeloid leukemiaGenomic fusion sequencesYears of ageTEL-AML1 translocationUtero originRemission samplesSecondary genetic alterationsGuthrie blood spotsBlood spotsGuthrie spotsPatientsLeukemiaLeukemia samplesGenetic alterationsRecent reportsFusion geneChildrenResultant fusion geneTranslocationInfantsUtero