biostudies-literatureZhou LNIA NIH HHSNIDDK NIH HHSNHLBI NIH HHSNCI NIH HHS25211-23https://www.ebi.ac.uk/biostudies/studies/S-EPMC3137092biostudies-literatureUnknown286(28)Myelodysplastic syndromes (MDS) are characterized by abnormal and dysplastic maturation of all blood lineages. Even though epigenetic alterations have been seen in MDS marrow progenitors, very little is known about the molecular alterations in dysplastic peripheral blood cells. We analyzed the methylome of MDS leukocytes by the HELP assay and determined that it was globally distinct from age-matched controls and was characterized by numerous novel, aberrant hypermethylated marks that were located mainly outside of CpG islands and preferentially affected GTPase regulators and other cancer-related pathways. Additionally, array comparative genomic hybridization revealed that novel as well as previously characterized deletions and amplifications could also be visualized in peripheral blood leuThe Journal of biological chemistryAberrant epigenetic and genetic marks are seen in myelodysplastic leukocytes and reveal Dock4 as a candidate pathogenic gene on chromosome 7q.PMC3137092T32 CA009173R01HL082846R01AG02913801K24 CA111717CA009173R01 HL082846P30 DK043351Kambhampati SBoultwood JMelnick ANischal SSauthararajah YSuzuki MZhang JHueck CSteidl UBhagat TOpalinska JAlencar CSohal DFreidman EVerma APlatanias LCMcMahon CYu YMo YAbdel-Wahab OParmar SZhou LYajnik VWickrema AGreally JMPellagatti AGore SDLevine RFigueroa MFazzari MfalseAberrant epigenetic and genetic marks are seen in myelodysplastic leukocytes and reveal Dock4 as a candidate pathogenic gene on chromosome 7q.Myelodysplastic syndromes (MDS) are characterized by abnormal and dysplastic maturation of all blood lineages. Even though epigenetic alterations have been seen in MDS marrow progenitors, very little is known about the molecular alterations in dysplastic peripheral blood cells. We analyzed the methylome of MDS leukocytes by the HELP assay and determined that it was globally distinct from age-matched controls and was characterized by numerous novel, aberrant hypermethylated marks that were located mainly outside of CpG islands and preferentially affected GTPase regulators and other cancer-related pathways. Additionally, array comparative genomic hybridization revealed that novel as well as previously characterized deletions and amplifications could also be visualized in peripheral blood leu2011-01-01T00:00:00Z2011 Jul2025-04-04T23:41:36.59Z2019-03-27T03:07:07ZS-EPMC31370922153203410.1074/jbc.M111.23502810.1074/jbc.m111.235028