fd5fa689c6e6c5510e4dfa98af5bd3c9 pmc_35008680.pdf 04937dc12b52bd8486dc13a5e679a74405f4c9ab pmc_35008680.pdf b3c5da958913cbb5561ffbb0ef5691c25f9b35282580f98bc13b243e16caa0e9 pmc_35008680.pdf Title: Histone Modifications and Their Targeting in Lymphoid Malignancies Subject: In a wide range of lymphoid neoplasms, the process of malignant transformation is associated with somatic mutations in B cells that affect the epigenetic machinery. Consequential alterations in histone modifications contribute to disease-specific changes in the transcriptional program. Affected genes commonly play important roles in cell cycle regulation, apoptosis-inducing signal transduction, and DNA damage response, thus facilitating the emergence of malignant traits that impair immune surveillance and favor the emergence of different B-cell lymphoma subtypes. In the last two decades, the field has made a major effort to develop therapies that target these epigenetic alterations. In this review, we discuss which epigenetic alterations occur in B-cell non-Hodgkin lymphoma. Furthermore, we aim to present in a close to comprehensive manner the current state-of-the-art in the preclinical and clinical development of epigenetic drugs. We focus on therapeutic strategies interfering with histone methylation and acetylation as these are most advanced in being deployed from the bench-to-bedside and have the greatest potential to improve the prognosis of lymphoma patients. Keywords: non-Hodgkin lymphoma; epigenetics; DNA methylation; HAT; HDAC; EZH2; bromodomain inhibitors; drug combination; clinical testing Author: Miranda Fernández-Serrano, René Winkler, Juliana C. Santos, Marguerite-Marie Le Pannérer, Marcus Buschbeck and Gaël Roué Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Dec 28 05:15:42 2021 CET ModDate: Tue Dec 28 05:28:10 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 31 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1455772 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- LSOMQK+URWPalladioL-Bold Type 1 Custom yes yes no 10 0 NBQMFX+URWPalladioL-Roma Type 1 Custom yes yes no 15 0 WMNEDU+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 GIFXFT+VnURWPalladioL-Bold Type 1 Custom yes yes no 23 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 32 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 36 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 40 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 52 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 55 0 BCAKEI+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 87 0 BCAKFJ+PalatinoLinotype TrueType WinAnsi yes yes no 90 0 BCAKFL+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 93 0 BCAKEI+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 110 0 BCAKFI+PalatinoLinotype CID TrueType Identity-H yes yes yes 113 0 BCAKFJ+PalatinoLinotype TrueType WinAnsi yes yes no 119 0 BCAKFL+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 122 0 KQBTEG+EURM10 Type 1 Builtin yes yes no 129 0 PDTLUH+CMSY10 Type 1 Builtin yes yes no 170 0 PWDRRF+VnURWPalladioL Type 1 Custom yes yes no 180 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 02:51:46 CEST RepresentationInformation: pmc_35008680.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 12:08:15 CEST Size: 1455772 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 871 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Children: Item: Title: Characteristics of the Main B-NHL Subtypes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Epigenetic Modification of Histone Proteins in B-NHL Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: The Pharmacological Targeting of Histone Acetylation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Children: Item: Title: Extensive Preclinical Development of HDAC Inhibitors Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Preclinical Evaluation of HATs as Targets for B-NHL Therapy Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Experimental Insight in the Utility BET Inhibitors Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Ongoing Clinical Development of HDACi, BETi and HATi Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Children: Item: Title: HDACi Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: HATi Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: BETi Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Targeting Histone Methylation and Some Other PTMs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Children: Item: Title: Preclinical Development of Histone Methyl Transferase and Demethylase Inhibitors Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: EZH2 Inhibitors in Clinical Development Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Targeting Other Posttranslational Modifications of Histones Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Conclusions and Future Directions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Info: Title: Histone Modifications and Their Targeting in Lymphoid Malignancies Author: Miranda Fernández-Serrano, René Winkler, Juliana C. Santos, Marguerite-Marie Le Pannérer, Marcus Buschbeck and Gaël Roué Subject: In a wide range of lymphoid neoplasms, the process of malignant transformation is associated with somatic mutations in B cells that affect the epigenetic machinery. Consequential alterations in histone modifications contribute to disease-specific changes in the transcriptional program. Affected genes commonly play important roles in cell cycle regulation, apoptosis-inducing signal transduction, and DNA damage response, thus facilitating the emergence of malignant traits that impair immune surveillance and favor the emergence of different B-cell lymphoma subtypes. In the last two decades, the field has made a major effort to develop therapies that target these epigenetic alterations. In this review, we discuss which epigenetic alterations occur in B-cell non-Hodgkin lymphoma. Furthermore, we aim to present in a close to comprehensive manner the current state-of-the-art in the preclinical and clinical development of epigenetic drugs. We focus on therapeutic strategies interfering with histone methylation and acetylation as these are most advanced in being deployed from the bench-to-bedside and have the greatest potential to improve the prognosis of lymphoma patients. 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