Epigenetics in focus: Pathogenesis-of myelodysplastic syndromes and the role of hypomethylating agents

Valeria Santini; Ari Melnick; Jaroslaw P. Maciejewski; Estelle Duprez; Clara Nervi; Lucio Cocco; Kevin G. Ford; Ghulam Mufti

doi:10.1016/j.critrevonc.2013.06.004

Epigenetics in focus: Pathogenesis-of myelodysplastic syndromes and the role of hypomethylating agents

Valeria Santini^*, Ari Melnick, Jaroslaw P. Maciejewski, Estelle Duprez, Clara Nervi, Lucio Cocco, Kevin G. Ford, Ghulam Mufti

^*Corresponding author for this work

Research output: Contribution to journal › Literature review › peer-review

26 Citations (Scopus)

Abstract

Dysregulation of cellular epigenetic machinery is considered a major pathogenetic determinant in many malignancies, including myelodysplastic syndromes (MDS). The importance of epigenetic dysfunction in MDS is reflected by the success of hypomethylating agents as standard of care for their treatment. Although these agents improve both survival and quality of life, knowledge gaps remain regarding the precise role of epigenetics in the pathogenesis of MDS and mechanisms by which hypomethylating agents exert their clinical effects. This article reviews the pathogenic role of epigenetic alterations in MDS, including the relationship between genetic and epigenetic abnormalities, and highlights emerging evidence that hypomethylating agents may reprogram the "methylome" while re-establishing hematopoiesis.

Original language	English
Pages (from-to)	231-245
Number of pages	15
Journal	Critical Reviews in Oncology/Hematology
Volume	88
Issue number	2
DOIs	https://doi.org/10.1016/j.critrevonc.2013.06.004
Publication status	Published - Nov 2013

Keywords

Myelodysplastic syndromes
Acute myeloid leukemia
Epigenetics
DNA hypermethylation
Hypomethylating agents
ACUTE MYELOID-LEUKEMIA
TRANS-RETINOIC ACID
CHRONIC MYELOMONOCYTIC LEUKEMIA
HISTONE DEACETYLASE INHIBITION
METHYLTRANSFERASE GENE EZH2
PROGNOSTIC SCORING SYSTEM
EMBRYONIC STEM-CELLS
DE-NOVO METHYLATION
DNA METHYLATION
VALPROIC ACID

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.critrevonc.2013.06.004

Cite this

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title = "Epigenetics in focus: Pathogenesis-of myelodysplastic syndromes and the role of hypomethylating agents",

abstract = "Dysregulation of cellular epigenetic machinery is considered a major pathogenetic determinant in many malignancies, including myelodysplastic syndromes (MDS). The importance of epigenetic dysfunction in MDS is reflected by the success of hypomethylating agents as standard of care for their treatment. Although these agents improve both survival and quality of life, knowledge gaps remain regarding the precise role of epigenetics in the pathogenesis of MDS and mechanisms by which hypomethylating agents exert their clinical effects. This article reviews the pathogenic role of epigenetic alterations in MDS, including the relationship between genetic and epigenetic abnormalities, and highlights emerging evidence that hypomethylating agents may reprogram the {"}methylome{"} while re-establishing hematopoiesis.",

keywords = "Myelodysplastic syndromes, Acute myeloid leukemia, Epigenetics, DNA hypermethylation, Hypomethylating agents, ACUTE MYELOID-LEUKEMIA, TRANS-RETINOIC ACID, CHRONIC MYELOMONOCYTIC LEUKEMIA, HISTONE DEACETYLASE INHIBITION, METHYLTRANSFERASE GENE EZH2, PROGNOSTIC SCORING SYSTEM, EMBRYONIC STEM-CELLS, DE-NOVO METHYLATION, DNA METHYLATION, VALPROIC ACID",

author = "Valeria Santini and Ari Melnick and Maciejewski, {Jaroslaw P.} and Estelle Duprez and Clara Nervi and Lucio Cocco and Ford, {Kevin G.} and Ghulam Mufti",

year = "2013",

month = nov,

doi = "10.1016/j.critrevonc.2013.06.004",

language = "English",

volume = "88",

pages = "231--245",

journal = "Critical Reviews in Oncology/Hematology",

issn = "1040-8428",

publisher = "Elsevier Ireland Ltd",

number = "2",

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TY - JOUR

T1 - Epigenetics in focus

T2 - Pathogenesis-of myelodysplastic syndromes and the role of hypomethylating agents

AU - Santini, Valeria

AU - Melnick, Ari

AU - Maciejewski, Jaroslaw P.

AU - Duprez, Estelle

AU - Nervi, Clara

AU - Cocco, Lucio

AU - Ford, Kevin G.

AU - Mufti, Ghulam

PY - 2013/11

Y1 - 2013/11

N2 - Dysregulation of cellular epigenetic machinery is considered a major pathogenetic determinant in many malignancies, including myelodysplastic syndromes (MDS). The importance of epigenetic dysfunction in MDS is reflected by the success of hypomethylating agents as standard of care for their treatment. Although these agents improve both survival and quality of life, knowledge gaps remain regarding the precise role of epigenetics in the pathogenesis of MDS and mechanisms by which hypomethylating agents exert their clinical effects. This article reviews the pathogenic role of epigenetic alterations in MDS, including the relationship between genetic and epigenetic abnormalities, and highlights emerging evidence that hypomethylating agents may reprogram the "methylome" while re-establishing hematopoiesis.

AB - Dysregulation of cellular epigenetic machinery is considered a major pathogenetic determinant in many malignancies, including myelodysplastic syndromes (MDS). The importance of epigenetic dysfunction in MDS is reflected by the success of hypomethylating agents as standard of care for their treatment. Although these agents improve both survival and quality of life, knowledge gaps remain regarding the precise role of epigenetics in the pathogenesis of MDS and mechanisms by which hypomethylating agents exert their clinical effects. This article reviews the pathogenic role of epigenetic alterations in MDS, including the relationship between genetic and epigenetic abnormalities, and highlights emerging evidence that hypomethylating agents may reprogram the "methylome" while re-establishing hematopoiesis.

KW - Myelodysplastic syndromes

KW - Acute myeloid leukemia

KW - Epigenetics

KW - DNA hypermethylation

KW - Hypomethylating agents

KW - ACUTE MYELOID-LEUKEMIA

KW - TRANS-RETINOIC ACID

KW - CHRONIC MYELOMONOCYTIC LEUKEMIA

KW - HISTONE DEACETYLASE INHIBITION

KW - METHYLTRANSFERASE GENE EZH2

KW - PROGNOSTIC SCORING SYSTEM

KW - EMBRYONIC STEM-CELLS

KW - DE-NOVO METHYLATION

KW - DNA METHYLATION

KW - VALPROIC ACID

U2 - 10.1016/j.critrevonc.2013.06.004

DO - 10.1016/j.critrevonc.2013.06.004

M3 - Literature review

SN - 1040-8428

VL - 88

SP - 231

EP - 245

JO - Critical Reviews in Oncology/Hematology

JF - Critical Reviews in Oncology/Hematology

IS - 2

ER -

Epigenetics in focus: Pathogenesis-of myelodysplastic syndromes and the role of hypomethylating agents

Abstract

Keywords

UN SDGs

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