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
Incorporation of DNA methylation quantitative trait loci (mQTLs) in epigenome-wide association analysis: application to birthweight effects in neonatal whole blood
Li S, Mancuso N, Metayer C, Ma X, de Smith A, Wiemels J. Incorporation of DNA methylation quantitative trait loci (mQTLs) in epigenome-wide association analysis: application to birthweight effects in neonatal whole blood. Clinical Epigenetics 2022, 14: 158. PMID: 36457128, PMCID: PMC9714153, DOI: 10.1186/s13148-022-01385-6.Peer-Reviewed Original ResearchMeSH KeywordsBirth WeightCpG IslandsDNA MethylationEpigenomeHumansInfant, NewbornQuantitative Trait LociConceptsMethylation quantitative trait lociSingle nucleotide polymorphismsDNA methylationGenetic variationDNA methylation quantitative trait lociGenetic effectsDiverse genetic ancestryEPIC arrayCpG island shore regionQuantitative trait lociDNA methylation dataEpigenome-wide association analysisTrait lociDevelopmental traitsEWAS resultsGenetic elementsGene expressionMethylation dataAssociation studiesK arrayAssociation analysisCertain lociMethylation levelsIllumina 450Top hitsInvestigating 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 ResearchConceptsEpigenome-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 DNAAccelerated epigenetic aging in newborns with Down syndrome
Xu K, Li S, Muskens IS, Elliott N, Myint SS, Pandey P, Hansen HM, Morimoto LM, Kang AY, Ma X, Metayer C, Mueller BA, Roberts I, Walsh KM, Horvath S, Wiemels JL, de Smith A. Accelerated epigenetic aging in newborns with Down syndrome. Aging Cell 2022, 21: e13652. PMID: 35661546, PMCID: PMC9282838, DOI: 10.1111/acel.13652.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgingAging, PrematureDNA MethylationDown SyndromeEpigenesis, GeneticEpigenomicsHumansInfant, NewbornConceptsDown syndromeAge accelerationEpigenetic age accelerationGestational age accelerationEarly-onset Alzheimer's diseaseTransient abnormal myelopoiesisPotential confounding factorsEpigenetic agingPremature agingSomatic GATA1 mutationsDS patientsAbnormal myelopoiesisBlood cell proportionsNewbornsAlzheimer's diseaseConfounding factorsBrain tissueCell proportionGATA1 mutationsEndocrine systemBloodTargeted sequencingSomatic mutationsSyndromeDisease
2021
The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis
Muskens IS, Li S, Jackson T, Elliot N, Hansen HM, Myint SS, Pandey P, Schraw JM, Roy R, Anguiano J, Goudevenou K, Siegmund KD, Lupo PJ, de Bruijn MFTR, Walsh KM, Vyas P, Ma X, Roy A, Roberts I, Wiemels JL, de Smith AJ. The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis. Nature Communications 2021, 12: 821. PMID: 33547282, PMCID: PMC7865055, DOI: 10.1038/s41467-021-21064-z.Peer-Reviewed Original ResearchMeSH KeywordsCase-Control StudiesCore Binding Factor Alpha 2 SubunitCpG IslandsDNA MethylationDown SyndromeEpigenesis, GeneticFemaleFetusGATA1 Transcription FactorGenome-Wide Association StudyGenome, HumanHematopoiesisHematopoietic Stem CellsHumansInfant, NewbornLiverMalePromoter Regions, GeneticProto-Oncogene Protein c-fli-1ConceptsDNA methylationGenome-wide impactGenome-wide effectsGenome-wide perturbationsPromoter/enhancer regionEpigenome-wide association studiesAssociation study resultsGene expression changesHematopoietic stem/progenitor cellsCell-type heterogeneityStem/progenitor cellsEpigenome-wide significant CpGsHematopoietic developmentDifferential methylationEpigenetic changesGene expressionPromoter regionEnhancer regionExpression changesAssociation studiesSignificant CpGsImportant regulatorSignificant hypermethylationHematopoietic cellsMethylation
2019
RBC transfusion independence among lower risk MDS patients receiving hypomethylating agents: a population-level analysis
Zeidan AM, Zhu W, Stahl M, Wang R, Huntington SF, Giri S, Podoltsev NA, Gore SD, Ma X, Davidoff AJ. RBC transfusion independence among lower risk MDS patients receiving hypomethylating agents: a population-level analysis. Leukemia & Lymphoma 2019, 60: 3181-3187. PMID: 31170846, DOI: 10.1080/10428194.2019.1622700.Peer-Reviewed Original ResearchConceptsRBC transfusion independenceLR-MDS patientsTransfusion independenceHMA initiationRBC transfusionClinical effectivenessReal-life clinical effectivenessRed blood cell transfusionLower-risk myelodysplastic syndromesLow-risk MDS patientsRisk MDS patientsBlood cell transfusionRisk myelodysplastic syndromesHMA therapyLR-MDSCell transfusionMost patientsDisease courseMDS patientsMedicare databaseMyelodysplastic syndromePopulation-level estimatesLower oddsTransfusionPatients
2017
Long-term survival of older patients with MDS treated with HMA therapy without subsequent stem cell transplantation
Zeidan AM, Stahl M, Hu X, Wang R, Huntington SF, Podoltsev NA, Gore SD, Ma X, Davidoff AJ. Long-term survival of older patients with MDS treated with HMA therapy without subsequent stem cell transplantation. Blood 2017, 131: 818-821. PMID: 29259002, PMCID: PMC6410557, DOI: 10.1182/blood-2017-10-811729.Peer-Reviewed Original ResearchParental Age and Risk of Pediatric Cancer in the Offspring: A Population-Based Record-Linkage Study in California
Wang R, Metayer C, Morimoto L, Wiemels JL, Yang J, DeWan AT, Kang A, Ma X. Parental Age and Risk of Pediatric Cancer in the Offspring: A Population-Based Record-Linkage Study in California. American Journal Of Epidemiology 2017, 186: 843-856. PMID: 28535175, PMCID: PMC5860074, DOI: 10.1093/aje/kwx160.Peer-Reviewed Original ResearchConceptsRecord linkage studyMaternal ageOdds ratioPediatric cancerParental agePopulation-based record linkage studyCentral nervous system tumorsRisk of lymphomaPopulation-based studyCancer registry dataNervous system tumorsRisk of leukemiaAge group 0Ages 0Pediatric cancer riskOlder paternal ageOlder age groupsTypes of cancerSystem tumorsRegistry dataCancer riskHigh riskGroup 0Birth recordsAge groups
2016
Modest improvement in survival of patients with refractory anemia with excess blasts in the hypomethylating agents era in the United States
Zeidan AM, Wang R, Gross CP, Gore SD, Huntington SF, Prebet T, Abel GA, Davidoff AJ, Ma X. Modest improvement in survival of patients with refractory anemia with excess blasts in the hypomethylating agents era in the United States. Leukemia & Lymphoma 2016, 58: 982-985. PMID: 27558206, DOI: 10.1080/10428194.2016.1214954.Peer-Reviewed Original Research
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
2010
Pattern of hypomethylating agents use among elderly patients with myelodysplastic syndromes
Wang R, Gross CP, Maggiore RJ, Halene S, Soulos PR, Raza A, Galili N, Ma X. Pattern of hypomethylating agents use among elderly patients with myelodysplastic syndromes. Leukemia Research 2010, 35: 904-908. PMID: 21067809, PMCID: PMC3114277, DOI: 10.1016/j.leukres.2010.10.007.Peer-Reviewed Original ResearchConceptsMyelodysplastic syndromePatient characteristicsRefractory anemiaMultivariate logistic regression modelMultiple patient characteristicsPopulation-based studyUse of HMAsLogistic regression modelsElderly patientsExcess blastsMultilineage dysplasiaRefractory cytopeniaMDS patientsPatientsComorbiditiesAnemiaSyndromeHigher chanceRegression modelsHMAsAgentsIntroduction periodCytopeniasDysplasiaCancer
2005
Molecular biomarkers for the study of childhood leukemia
Smith MT, McHale CM, Wiemels JL, Zhang L, Wiencke JK, Zheng S, Gunn L, Skibola CF, Ma X, Buffler PA. Molecular biomarkers for the study of childhood leukemia. Toxicology And Applied Pharmacology 2005, 206: 237-245. PMID: 15967214, DOI: 10.1016/j.taap.2004.11.026.Peer-Reviewed Original ResearchConceptsAcute myeloid leukemiaAcute lymphocytic leukemiaChildhood leukemiaLeukemia riskChildhood acute lymphocytic leukemiaC609T polymorphismLow folate intakeNeonatal blood spotsYears of lifeMethylenetetrahydrofolate reductase (MTHFR) geneDifferent cytogenetic subgroupsPerinatal exposureFolate intakeMyeloid leukemiaLymphocytic leukemiaT polymorphismUseful biomarkerInfectious agentsAberrant gene methylationLeukemiaCytogenetic subgroupsBlood spotsMolecular biomarkersIndoor pesticidesGene methylation
2004
Hypermethylation of the 5′ CpG Island of the FHIT Gene Is Associated with Hyperdiploid and Translocation-Negative Subtypes of Pediatric Leukemia
Zheng S, Ma X, Zhang L, Gunn L, Smith MT, Wiemels JL, Leung K, Buffler PA, Wiencke JK. Hypermethylation of the 5′ CpG Island of the FHIT Gene Is Associated with Hyperdiploid and Translocation-Negative Subtypes of Pediatric Leukemia. Cancer Research 2004, 64: 2000-2006. PMID: 15026336, DOI: 10.1158/0008-5472.can-03-2387.Peer-Reviewed Original ResearchMeSH KeywordsAcid Anhydride HydrolasesAdolescentAntimetabolites, AntineoplasticAzacitidineB-LymphocytesChildChild, PreschoolChromosomes, Human, Pair 12Chromosomes, Human, Pair 21CpG IslandsDecitabineDiploidyDNA MethylationDNA, NeoplasmFemaleGene DeletionGene Expression Regulation, NeoplasticHumansLeukemia, MyeloidMaleNeoplasm ProteinsPrecursor Cell Lymphoblastic Leukemia-LymphomaPromoter Regions, GeneticT-LymphocytesTranslocation, GeneticTumor Cells, CulturedConceptsPediatric leukemiaFHIT geneB cellsLeukemia cell linesFHIT methylation statusHigh WBC countPopulation-based casesChildhood leukemia patientsCell linesHyperdiploid B cellsHypermethylation of FHITPrognostic indicatorWBC countMethylation-specific PCRLeukemia patientsMyeloid leukemiaCytogenetic subtypesLoss of heterozygosityBone marrowFHIT expressionPrimary leukemiasFHIT inactivationFHIT methylationHuman malignanciesLeukemia