title: The epigenome of AML stem and progenitor cells.
abstract: Acute myeloid leukemia (AML) is sustained by a population of cancer stem cells (CSCs or cancer-initiating cell). The mechanisms underlying switches from CSCs to non-CSCs in vivo remain to be understood. We address this issue in AML from the aspect of epigenetics using genome-wide screening for DNA methylation and selected histone modifications. We found no major differences in DNA methylation, especially in promoter CpG islands, between CSCs and non-CSCs. By contrast, we found thousands of genes that change H3K4me3 and/or H3K27me3 status between stem and progenitor cells as well as between progenitor and mature cells. Stem cell related pathways and proliferation or metabolism related pathways characterize genes differentially enriched for H3K4me3/H3K27me3 in stem and progenitor populations. Bivalent genes in stem cells are more plastic during differentiation and are more likely to lose H3K4me3 than to lose H3K27me3, consistent with increasingly closed chromatin state with differentiation. Our data indicates that histone modifications but not promoter DNA methylation are involved in switches from CSCs to non-CSCs in AML.
authors.affiliation: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jumpei
authors.initials: J
authors.lastname: Yamazaki
authors.forename: Marcos R
authors.initials: MR
authors.lastname: Estecio
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.forename: Hai
authors.initials: H
authors.lastname: Long
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Malouf
authors.forename: David
authors.initials: D
authors.lastname: Graber
authors.forename: Yujia
authors.initials: Y
authors.lastname: Huo
authors.forename: Louis
authors.initials: L
authors.lastname: Ramagli
authors.forename: Shoudan
authors.initials: S
authors.lastname: Liang
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kornblau
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Jelinek
authors.forename: Jean-Pierre J
authors.initials: JP
authors.lastname: Issa
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D015973:Gene Expression Regulation, Leukemic; D006657:Histones / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D011499:Protein Processing, Post-Translational / Q000235:genetics; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones