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Cancers
Special Issues
Multi-Faceted Epigenetic Dysregulation in Acute Myeloid Leukemia
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Multi-Faceted Epigenetic Dysregulation in Acute Myeloid Leukemia

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: closed (23 August 2024) | Viewed by 7434

Special Issue Editors

Dr. Shuchi Agrawal-Singh

E-Mail Website1 Website2
Guest Editor
Wellcome Trust—Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 1TN, UK
Interests: dysregulated epigenetic language in leukemia and when/how it is miswritten, mis-erased, or misinterpreted; chromatin modification; histone; DNA methylation; epigenetics; leukemia; transcription factors; mutations in AML
Dr. Stefanie Göllner

E-Mail Website
Guest Editor
Department of Medicine V-Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
Interests: AG Epigenenomics; Epitranscriptomics and novel therapy approaches in AML

Special Issue Information

Dear Colleagues,

AML is a complex heterogenous disease characterized by the presence of highly proliferative myeloid progenitor cells with reduced capacity to differentiate. Recent advanced understanding combining knowledge about recurring genetic mutations and epigenetic alterations suggests that AML is an epigenetic disease, mainly because the disease is driven by driving/recurring mutations in epigenetic modulators, DNA/chromatin modifiers (DNMT3A, TET2, IDH1, IDH2, EZH2, KDM6A, ASXL1, PHF6, and others), RNA modifiers (METTL3, METTL14, FTO, ALKBH5, YTHDF1/2), RNA splicing (SRSF2, SF3B1, U2AF1, and ZRSR2), 3D chromosomal interactions (CTCF and the Cohesin complex), and chromatin remodeling complexes SWI/SNF and NPM1. Many of these regulatory processes consist of multiple enzymes and are probably interconnected. Moreover, the role of IDR (intrinsically disordered region) in oncoproteins such as NUP98-HOXA9 or UTX to form liquid condensate that controls transcription and genome architecture has provided new insights for epigenetic understanding in AML. Identifying these cross-talks and numerous novel epi-mechanisms contributing towards leukemogenesis and defining the cause for the altered epigenome will hopefully open new avenues for improved therapeutic approaches.

We are pleased to invite you to contribute to this Special Issue of Cancers, entitled “Multi-Faceted Epigenetic Dysregulation in Acute Myeloid Leukemia”. This Special Issue aims to bring together the state-of-the-art research in the field covering various angles of epi-mechanisms that are dysregulated in AML.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: chromatin regulation, nuclear topology and 3D chromatin architecture, liquid condensates and phase separation, epi-mechanisms, RNA modifications, epi-metabolism.

I look forward to receiving your contributions.

Dr. Shuchi Agrawal-Singh
Dr. Stefanie Göllner
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • DNA/histone modifications
  • chromatin regulators
  • transcriptional control
  • enhancers and cis regulatory elements
  • intrinsically disordered region (IDR)
  • nuclear architecture
  • metabolism

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Published Papers (2 papers)

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Review

16 pages, 5579 KiB  
Review
Polycomb Alterations in Acute Myeloid Leukaemia: From Structure to Function
by Teerna Bhattacharyya and Jonathan Bond
Cancers 2023, 15(6), 1693; https://doi.org/10.3390/cancers15061693 - 9 Mar 2023
Viewed by 2863
Abstract
Epigenetic dysregulation is a hallmark of many haematological malignancies and is very frequent in acute myeloid leukaemia (AML). A cardinal example is the altered activity of the Polycomb Repressive Complex 2 (PRC2) due to somatic mutations and deletions in genes encoding PRC2 core [...] Read more.
Epigenetic dysregulation is a hallmark of many haematological malignancies and is very frequent in acute myeloid leukaemia (AML). A cardinal example is the altered activity of the Polycomb Repressive Complex 2 (PRC2) due to somatic mutations and deletions in genes encoding PRC2 core factors that are necessary for correct complex assembly. These genetic alterations typically lead to reduced histone methyltransferase activity that, in turn, has been strongly linked to poor prognosis and chemoresistance. In this review, we provide an overview of genetic alterations of PRC components in AML, with particular reference to structural and functional features of PRC2 factors. We further review genetic interactions between these alterations and other AML-associated mutations in both adult and paediatric leukaemias. Finally, we discuss reported prognostic links between PRC2 mutations and deletions and disease outcomes and potential implications for therapy. Full article
(This article belongs to the Special Issue Multi-Faceted Epigenetic Dysregulation in Acute Myeloid Leukemia)
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17 pages, 1272 KiB  
Review
Viewing AML through a New Lens: Technological Advances in the Study of Epigenetic Regulation
by Laura C. Godfrey and Alba Rodriguez-Meira
Cancers 2022, 14(23), 5989; https://doi.org/10.3390/cancers14235989 - 4 Dec 2022
Viewed by 3496
Abstract
Epigenetic modifications, such as histone modifications and DNA methylation, are essential for ensuring the dynamic control of gene regulation in every cell type. These modifications are associated with gene activation or repression, depending on the genomic context and specific type of modification. In [...] Read more.
Epigenetic modifications, such as histone modifications and DNA methylation, are essential for ensuring the dynamic control of gene regulation in every cell type. These modifications are associated with gene activation or repression, depending on the genomic context and specific type of modification. In both cases, they are deposited and removed by epigenetic modifier proteins. In acute myeloid leukemia (AML), the function of these proteins is perturbed through genetic mutations (i.e., in the DNA methylation machinery) or translocations (i.e., MLL-rearrangements) arising during leukemogenesis. This can lead to an imbalance in the epigenomic landscape, which drives aberrant gene expression patterns. New technological advances, such as CRISPR editing, are now being used to precisely model genetic mutations and chromosomal translocations. In addition, high-precision epigenomic editing using dCas9 or CRISPR base editing are being used to investigate the function of epigenetic mechanisms in gene regulation. To interrogate these mechanisms at higher resolution, advances in single-cell techniques have begun to highlight the heterogeneity of epigenomic landscapes and how these impact on gene expression within different AML populations in individual cells. Combined, these technologies provide a new lens through which to study the role of epigenetic modifications in normal hematopoiesis and how the underlying mechanisms can be hijacked in the context of malignancies such as AML. Full article
(This article belongs to the Special Issue Multi-Faceted Epigenetic Dysregulation in Acute Myeloid Leukemia)
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