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HSC commitment-associated epigenetic signature is prognostic in acute myeloid leukemia

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HSC commitment-associated epigenetic signature is prognostic in acute myeloid leukemia. / Bartholdy, Boris; Christopeit, Maximilian; Will, Britta; Mo, Yongkai; Barreyro, Laura; Yu, Yiting; Bhagat, Tushar D; Okoye-Okafor, Ujunwa C; Todorova, Tihomira I; Greally, John M; Levine, Ross L; Melnick, Ari; Verma, Amit; Steidl, Ulrich.

In: J CLIN INVEST, Vol. 124, No. 3, 01.03.2014, p. 1158-67.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Bartholdy, B, Christopeit, M, Will, B, Mo, Y, Barreyro, L, Yu, Y, Bhagat, TD, Okoye-Okafor, UC, Todorova, TI, Greally, JM, Levine, RL, Melnick, A, Verma, A & Steidl, U 2014, 'HSC commitment-associated epigenetic signature is prognostic in acute myeloid leukemia', J CLIN INVEST, vol. 124, no. 3, pp. 1158-67. https://doi.org/10.1172/JCI71264

APA

Bartholdy, B., Christopeit, M., Will, B., Mo, Y., Barreyro, L., Yu, Y., Bhagat, T. D., Okoye-Okafor, U. C., Todorova, T. I., Greally, J. M., Levine, R. L., Melnick, A., Verma, A., & Steidl, U. (2014). HSC commitment-associated epigenetic signature is prognostic in acute myeloid leukemia. J CLIN INVEST, 124(3), 1158-67. https://doi.org/10.1172/JCI71264

Vancouver

Bartholdy B, Christopeit M, Will B, Mo Y, Barreyro L, Yu Y et al. HSC commitment-associated epigenetic signature is prognostic in acute myeloid leukemia. J CLIN INVEST. 2014 Mar 1;124(3):1158-67. https://doi.org/10.1172/JCI71264

Bibtex

@article{ba03b4cf9ced47dd995bda212e7a9c6c,
title = "HSC commitment-associated epigenetic signature is prognostic in acute myeloid leukemia",
abstract = "Acute myeloid leukemia (AML) is characterized by disruption of HSC and progenitor cell differentiation. Frequently, AML is associated with mutations in genes encoding epigenetic modifiers. We hypothesized that analysis of alterations in DNA methylation patterns during healthy HSC commitment and differentiation would yield epigenetic signatures that could be used to identify stage-specific prognostic subgroups of AML. We performed a nano HpaII-tiny-fragment-enrichment-by-ligation-mediated-PCR (nanoHELP) assay to compare genome-wide cytosine methylation profiles between highly purified human long-term HSC, short-term HSC, common myeloid progenitors, and megakaryocyte-erythrocyte progenitors. We observed that the most striking epigenetic changes occurred during the commitment of short-term HSC to common myeloid progenitors and these alterations were predominantly characterized by loss of methylation. We developed a metric of the HSC commitment–associated methylation pattern that proved to be highly prognostic of overall survival in 3 independent large AML patient cohorts, regardless of patient treatment and epigenetic mutations. Application of the epigenetic signature metric for AML prognosis was superior to evaluation of commitment-based gene expression signatures. Together, our data define a stem cell commitment–associated methylome that is independently prognostic of poorer overall survival in AML.",
keywords = "Cell Differentiation, DNA Methylation, Epigenesis, Genetic, Hematopoietic Stem Cells, Humans, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute, Prognosis, Proportional Hazards Models, Transcriptome",
author = "Boris Bartholdy and Maximilian Christopeit and Britta Will and Yongkai Mo and Laura Barreyro and Yiting Yu and Bhagat, {Tushar D} and Okoye-Okafor, {Ujunwa C} and Todorova, {Tihomira I} and Greally, {John M} and Levine, {Ross L} and Ari Melnick and Amit Verma and Ulrich Steidl",
note = "Keine Zugeh{\"o}rigkeit zum UKE laut WOS. Geteilte Erstautorenschaft gepr{\"u}ft. http://www.jci.org/articles/view/71264 ",
year = "2014",
month = mar,
day = "1",
doi = "10.1172/JCI71264",
language = "English",
volume = "124",
pages = "1158--67",
journal = "J CLIN INVEST",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "3",

}

RIS

TY - JOUR

T1 - HSC commitment-associated epigenetic signature is prognostic in acute myeloid leukemia

AU - Bartholdy, Boris

AU - Christopeit, Maximilian

AU - Will, Britta

AU - Mo, Yongkai

AU - Barreyro, Laura

AU - Yu, Yiting

AU - Bhagat, Tushar D

AU - Okoye-Okafor, Ujunwa C

AU - Todorova, Tihomira I

AU - Greally, John M

AU - Levine, Ross L

AU - Melnick, Ari

AU - Verma, Amit

AU - Steidl, Ulrich

N1 - Keine Zugehörigkeit zum UKE laut WOS. Geteilte Erstautorenschaft geprüft. http://www.jci.org/articles/view/71264

PY - 2014/3/1

Y1 - 2014/3/1

N2 - Acute myeloid leukemia (AML) is characterized by disruption of HSC and progenitor cell differentiation. Frequently, AML is associated with mutations in genes encoding epigenetic modifiers. We hypothesized that analysis of alterations in DNA methylation patterns during healthy HSC commitment and differentiation would yield epigenetic signatures that could be used to identify stage-specific prognostic subgroups of AML. We performed a nano HpaII-tiny-fragment-enrichment-by-ligation-mediated-PCR (nanoHELP) assay to compare genome-wide cytosine methylation profiles between highly purified human long-term HSC, short-term HSC, common myeloid progenitors, and megakaryocyte-erythrocyte progenitors. We observed that the most striking epigenetic changes occurred during the commitment of short-term HSC to common myeloid progenitors and these alterations were predominantly characterized by loss of methylation. We developed a metric of the HSC commitment–associated methylation pattern that proved to be highly prognostic of overall survival in 3 independent large AML patient cohorts, regardless of patient treatment and epigenetic mutations. Application of the epigenetic signature metric for AML prognosis was superior to evaluation of commitment-based gene expression signatures. Together, our data define a stem cell commitment–associated methylome that is independently prognostic of poorer overall survival in AML.

AB - Acute myeloid leukemia (AML) is characterized by disruption of HSC and progenitor cell differentiation. Frequently, AML is associated with mutations in genes encoding epigenetic modifiers. We hypothesized that analysis of alterations in DNA methylation patterns during healthy HSC commitment and differentiation would yield epigenetic signatures that could be used to identify stage-specific prognostic subgroups of AML. We performed a nano HpaII-tiny-fragment-enrichment-by-ligation-mediated-PCR (nanoHELP) assay to compare genome-wide cytosine methylation profiles between highly purified human long-term HSC, short-term HSC, common myeloid progenitors, and megakaryocyte-erythrocyte progenitors. We observed that the most striking epigenetic changes occurred during the commitment of short-term HSC to common myeloid progenitors and these alterations were predominantly characterized by loss of methylation. We developed a metric of the HSC commitment–associated methylation pattern that proved to be highly prognostic of overall survival in 3 independent large AML patient cohorts, regardless of patient treatment and epigenetic mutations. Application of the epigenetic signature metric for AML prognosis was superior to evaluation of commitment-based gene expression signatures. Together, our data define a stem cell commitment–associated methylome that is independently prognostic of poorer overall survival in AML.

KW - Cell Differentiation

KW - DNA Methylation

KW - Epigenesis, Genetic

KW - Hematopoietic Stem Cells

KW - Humans

KW - Kaplan-Meier Estimate

KW - Leukemia, Myeloid, Acute

KW - Prognosis

KW - Proportional Hazards Models

KW - Transcriptome

U2 - 10.1172/JCI71264

DO - 10.1172/JCI71264

M3 - SCORING: Journal article

C2 - 24487588

VL - 124

SP - 1158

EP - 1167

JO - J CLIN INVEST

JF - J CLIN INVEST

SN - 0021-9738

IS - 3

ER -