The epigenome of AML stem and progenitor cells

Jumpei Yamazaki; Marcos R. Estecio; Yue Lu; Hai Long; Gabriel G. Malouf; David Graber; Yujia Huo; Louis Ramagli; Shoudan Liang; Steven M. Kornblau; Jaroslav Jelinek; Jean Pierre J. Issa

doi:10.4161/epi.23243

The epigenome of AML stem and progenitor cells

Jumpei Yamazaki, Marcos R. Estecio, Yue Lu, Hai Long, Gabriel G. Malouf, David Graber, Yujia Huo, Louis Ramagli, Shoudan Liang, Steven M. Kornblau, Jaroslav Jelinek, Jean Pierre J. Issa

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39 Scopus citations

Abstract

Acute myeloid leukemia (AML) is sustained by a population of cancer stem cells (CSC s or cancer-initiating cell). The mechanisms underlying switches from CSC s to non-CSC s 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 CSC s and non-CSC s. 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 CSC s to non-CSC s in AML.

Original language	English (US)
Pages (from-to)	92-104
Number of pages	13
Journal	Epigenetics
Volume	8
Issue number	1
DOIs	https://doi.org/10.4161/epi.23243
State	Published - Jan 2013

Keywords

AML
DNA methylation
Histone modification
Progenitor
Stem

ASJC Scopus subject areas

Molecular Biology
Cancer Research

MD Anderson CCSG core facilities

Advanced Technology Genomics Core
Bioinformatics Shared Resource

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10.4161/epi.23243

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title = "The epigenome of AML stem and progenitor cells",

abstract = "Acute myeloid leukemia (AML) is sustained by a population of cancer stem cells (CSC s or cancer-initiating cell). The mechanisms underlying switches from CSC s to non-CSC s 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 CSC s and non-CSC s. 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 CSC s to non-CSC s in AML.",

keywords = "AML, DNA methylation, Histone modification, Progenitor, Stem",

author = "Jumpei Yamazaki and Estecio, {Marcos R.} and Yue Lu and Hai Long and Malouf, {Gabriel G.} and David Graber and Yujia Huo and Louis Ramagli and Shoudan Liang and Kornblau, {Steven M.} and Jaroslav Jelinek and Issa, {Jean Pierre J.}",

note = "Funding Information: The authors thank the patients who have contributed to our understanding of these disorders. This work was supported by National Institutes of Health grants CA100632, CA121104 and CA046939 and supported by a Stand Up to Cancer grant from the American Association for Cancer Research. J.P.I. is an American Cancer Society Clinical Research professor supported by a generous gift from the F.M. Kirby Foundation.",

year = "2013",

month = jan,

doi = "10.4161/epi.23243",

language = "English (US)",

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T1 - The epigenome of AML stem and progenitor cells

AU - Yamazaki, Jumpei

AU - Estecio, Marcos R.

AU - Lu, Yue

AU - Long, Hai

AU - Malouf, Gabriel G.

AU - Graber, David

AU - Huo, Yujia

AU - Ramagli, Louis

AU - Liang, Shoudan

AU - Kornblau, Steven M.

AU - Jelinek, Jaroslav

AU - Issa, Jean Pierre J.

N1 - Funding Information: The authors thank the patients who have contributed to our understanding of these disorders. This work was supported by National Institutes of Health grants CA100632, CA121104 and CA046939 and supported by a Stand Up to Cancer grant from the American Association for Cancer Research. J.P.I. is an American Cancer Society Clinical Research professor supported by a generous gift from the F.M. Kirby Foundation.

PY - 2013/1

Y1 - 2013/1

N2 - Acute myeloid leukemia (AML) is sustained by a population of cancer stem cells (CSC s or cancer-initiating cell). The mechanisms underlying switches from CSC s to non-CSC s 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 CSC s and non-CSC s. 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 CSC s to non-CSC s in AML.

AB - Acute myeloid leukemia (AML) is sustained by a population of cancer stem cells (CSC s or cancer-initiating cell). The mechanisms underlying switches from CSC s to non-CSC s 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 CSC s and non-CSC s. 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 CSC s to non-CSC s in AML.

KW - AML

KW - DNA methylation

KW - Histone modification

KW - Progenitor

KW - Stem

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The epigenome of AML stem and progenitor cells

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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