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The Role of Histone Protein Modifications and Mutations in Histone Modifiers in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia

While cancer has been long recognized as a disease of the genome, the importance of epigenetic mechanisms in neoplasia was acknowledged more recently. The most active epigenetic marks are DNA methylation and histone protein modifications and they are involved in basic biological phenomena in every c...

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Autores principales: Janczar, Szymon, Janczar, Karolina, Pastorczak, Agata, Harb, Hani, Paige, Adam J. W., Zalewska-Szewczyk, Beata, Danilewicz, Marian, Mlynarski, Wojciech
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295773/
https://www.ncbi.nlm.nih.gov/pubmed/28054944
http://dx.doi.org/10.3390/cancers9010002
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author Janczar, Szymon
Janczar, Karolina
Pastorczak, Agata
Harb, Hani
Paige, Adam J. W.
Zalewska-Szewczyk, Beata
Danilewicz, Marian
Mlynarski, Wojciech
author_facet Janczar, Szymon
Janczar, Karolina
Pastorczak, Agata
Harb, Hani
Paige, Adam J. W.
Zalewska-Szewczyk, Beata
Danilewicz, Marian
Mlynarski, Wojciech
author_sort Janczar, Szymon
collection PubMed
description While cancer has been long recognized as a disease of the genome, the importance of epigenetic mechanisms in neoplasia was acknowledged more recently. The most active epigenetic marks are DNA methylation and histone protein modifications and they are involved in basic biological phenomena in every cell. Their role in tumorigenesis is stressed by recent unbiased large-scale studies providing evidence that several epigenetic modifiers are recurrently mutated or frequently dysregulated in multiple cancers. The interest in epigenetic marks is especially due to the fact that they are potentially reversible and thus druggable. In B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) there is a relative paucity of reports on the role of histone protein modifications (acetylation, methylation, phosphorylation) as compared to acute myeloid leukemia, T-cell ALL, or other hematologic cancers, and in this setting chromatin modifications are relatively less well studied and reviewed than DNA methylation. In this paper, we discuss the biomarker associations and evidence for a driver role of dysregulated global and loci-specific histone marks, as well as mutations in epigenetic modifiers in BCP-ALL. Examples of chromatin modifiers recurrently mutated/disrupted in BCP-ALL and associated with disease outcomes include MLL1, CREBBP, NSD2, and SETD2. Altered histone marks and histone modifiers and readers may play a particular role in disease chemoresistance and relapse. We also suggest that epigenetic regulation of B-cell differentiation may have parallel roles in leukemogenesis.
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spelling pubmed-52957732017-02-08 The Role of Histone Protein Modifications and Mutations in Histone Modifiers in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia Janczar, Szymon Janczar, Karolina Pastorczak, Agata Harb, Hani Paige, Adam J. W. Zalewska-Szewczyk, Beata Danilewicz, Marian Mlynarski, Wojciech Cancers (Basel) Review While cancer has been long recognized as a disease of the genome, the importance of epigenetic mechanisms in neoplasia was acknowledged more recently. The most active epigenetic marks are DNA methylation and histone protein modifications and they are involved in basic biological phenomena in every cell. Their role in tumorigenesis is stressed by recent unbiased large-scale studies providing evidence that several epigenetic modifiers are recurrently mutated or frequently dysregulated in multiple cancers. The interest in epigenetic marks is especially due to the fact that they are potentially reversible and thus druggable. In B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) there is a relative paucity of reports on the role of histone protein modifications (acetylation, methylation, phosphorylation) as compared to acute myeloid leukemia, T-cell ALL, or other hematologic cancers, and in this setting chromatin modifications are relatively less well studied and reviewed than DNA methylation. In this paper, we discuss the biomarker associations and evidence for a driver role of dysregulated global and loci-specific histone marks, as well as mutations in epigenetic modifiers in BCP-ALL. Examples of chromatin modifiers recurrently mutated/disrupted in BCP-ALL and associated with disease outcomes include MLL1, CREBBP, NSD2, and SETD2. Altered histone marks and histone modifiers and readers may play a particular role in disease chemoresistance and relapse. We also suggest that epigenetic regulation of B-cell differentiation may have parallel roles in leukemogenesis. MDPI 2017-01-03 /pmc/articles/PMC5295773/ /pubmed/28054944 http://dx.doi.org/10.3390/cancers9010002 Text en © 2017 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Janczar, Szymon
Janczar, Karolina
Pastorczak, Agata
Harb, Hani
Paige, Adam J. W.
Zalewska-Szewczyk, Beata
Danilewicz, Marian
Mlynarski, Wojciech
The Role of Histone Protein Modifications and Mutations in Histone Modifiers in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia
title The Role of Histone Protein Modifications and Mutations in Histone Modifiers in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia
title_full The Role of Histone Protein Modifications and Mutations in Histone Modifiers in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia
title_fullStr The Role of Histone Protein Modifications and Mutations in Histone Modifiers in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia
title_full_unstemmed The Role of Histone Protein Modifications and Mutations in Histone Modifiers in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia
title_short The Role of Histone Protein Modifications and Mutations in Histone Modifiers in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia
title_sort role of histone protein modifications and mutations in histone modifiers in pediatric b-cell progenitor acute lymphoblastic leukemia
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295773/
https://www.ncbi.nlm.nih.gov/pubmed/28054944
http://dx.doi.org/10.3390/cancers9010002
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