446fbe504fc53a5e864ea9858774c22d 270647.pdf f07f775e116e6a07e28e0da23a6f1f70c65c4e45 270647.pdf 61ee56c976e8388c148b81afef014a7d1ddbc5384ea9dd230cf5a752bb204fe6 270647.pdf Title: Epigenetics in a Spectrum of Myeloid Diseases and Its Exploitation for Therapy Subject: Mutations in genes encoding chromatin regulators are early events contributing to developing asymptomatic clonal hematopoiesis of indeterminate potential and its frequent progression to myeloid diseases with increasing severity. We focus on the subset of myeloid diseases encompassing myelodysplastic syndromes and their transformation to secondary acute myeloid leukemia. We introduce the major concepts of chromatin regulation that provide the basis of epigenetic regulation. In greater detail, we discuss those chromatin regulators that are frequently mutated in myelodysplastic syndromes. We discuss their role in the epigenetic regulation of normal hematopoiesis and the consequence of their mutation. Finally, we provide an update on the drugs interfering with chromatin regulation approved or in development for myelodysplastic syndromes and acute myeloid leukemia. Keywords: epigenetics; chromatin; epigenetic regulators; clonal hematopoiesis of indeterminate potential (CHIP); myelodysplastic syndromes (MDS); acute myeloid leukemia (AML); secondary acute myeloid leukemia (sAML) Author: Michael Maher, Jeannine Diesch, Marguerite-Marie Le Pannérer and Marcus Buschbeck Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Apr 8 08:11:28 2021 CEST ModDate: Fri Apr 9 06:01:01 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 27 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1429498 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BTFGED+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 TLJYFN+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 BEXKSN+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 SAYKPE+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 33 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 55 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 59 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 63 0 AOPHAZ+CMSY10 Type 1 Builtin yes yes no 102 0 CKBPVA+EURM10 Type 1 Builtin yes yes no 128 0 EENAOP+VnURWPalladioL Type 1 Custom yes yes no 138 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 03:07:30 CEST RepresentationInformation: 270647.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-05-26 17:20:10 CEST Size: 1429498 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 729 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: CHIP-MDS-sAML A Spectrum Myeloid Diseases Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Modifications of Chromatin Are the Molecular Basis of Epigenetic Regulation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Epigenetic Regulators Frequently Mutated in Myeloid Diseases and Their Function Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Children: Item: Title: Mutations Causing Aberrant DNA Methylation TET2, DNMT3A, IDH Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Dysregulation of Histone Modifications EZH2, RUNX1, BCOR, ASXL1 Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Altering Chromatin Structure The Cohesin Complex Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Epigenetic Drugs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: Azanucleosides Are DNA Hypomethylating Agents and More Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Targeting Histone Acetylation and Active Transcription Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Targeting Histone Deacetylation and Gene Repression Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Reversing Metabolic Change with IDH Inhibitors Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Targeting Histone Methylation with Inhibitors of Histone Methylases and Demethylases Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Info: Title: Epigenetics in a Spectrum of Myeloid Diseases and Its Exploitation for Therapy Author: Michael Maher, Jeannine Diesch, Marguerite-Marie Le Pannérer and Marcus Buschbeck Subject: Mutations in genes encoding chromatin regulators are early events contributing to developing asymptomatic clonal hematopoiesis of indeterminate potential and its frequent progression to myeloid diseases with increasing severity. We focus on the subset of myeloid diseases encompassing myelodysplastic syndromes and their transformation to secondary acute myeloid leukemia. We introduce the major concepts of chromatin regulation that provide the basis of epigenetic regulation. In greater detail, we discuss those chromatin regulators that are frequently mutated in myelodysplastic syndromes. We discuss their role in the epigenetic regulation of normal hematopoiesis and the consequence of their mutation. Finally, we provide an update on the drugs interfering with chromatin regulation approved or in development for myelodysplastic syndromes and acute myeloid leukemia. Keywords: epigenetics; chromatin; epigenetic regulators; clonal hematopoiesis of indeterminate potential (CHIP); myelodysplastic syndromes (MDS); acute myeloid leukemia (AML); secondary acute myeloid leukemia (sAML) Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Apr 08 08:11:28 CEST 2021 ModDate: Fri Apr 09 06:01:01 CEST 2021 ID: 0xc8824e8a9b8053fad1dd309e7e8b7ec1, 0xc8824e8a9b8053fad1dd309e7e8b7ec1 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: CKBPVA+EURM10 FontSubset: true FirstChar: 11 LastChar: 11 FontDescriptor: FontName: CKBPVA+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: BEXKSN+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 151 FontDescriptor: FontName: BEXKSN+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: AOPHAZ+CMSY10 FontSubset: true FirstChar: 48 LastChar: 48 FontDescriptor: FontName: 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