5a977571561d3fb879c1f0d26eaea104 ijms-22-03127-v2.pdf 1cf196ef3d04bb71e45cd2afb09902905323029e ijms-22-03127-v2.pdf ee076f47a0aa208d94e7308c0e26ca45117774936d987d45531c76036884b3fa ijms-22-03127-v2.pdf Title: Epigenetic Control of Infant B Cell Precursor Acute Lymphoblastic Leukemia Subject: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a highly aggressive malignancy, with poorer prognosis in infants than in adults. A genetic signature has been associated with this outcome but, remarkably, leukemogenesis is commonly triggered by genetic alterations of embryonic origin that involve the deregulation of chromatin remodelers. This review considers in depth how the alteration of epigenetic profiles (at DNA and histone levels) induces an aberrant phenotype in B lymphocyte progenitors by modulating the oncogenic drivers and tumor suppressors involved in key cancer hallmarks. DNA methylation patterns have been widely studied in BCP-ALL and their correlation with survival has been established. However, the effect of methylation on histone residues can be very different. For instance, methyltransferase KMT2A gene participates in chromosomal rearrangements with several partners, imposing an altered pattern of methylated H3K4 and H3K79 residues, enhancing oncogene promoter activation, and conferring a worse outcome on affected infants. In parallel, acetylation processes provide an additional layer of epigenetic regulation and can alter the chromatin conformation, enabling the binding of regulatory factors. Therefore, an integrated knowledge of all epigenetic disorders is essential to understand the molecular basis of BCP-ALL and to identify novel entry points that can be exploited to improve therapeutic options and disease prognosis. Keywords: epigenetics; acute lymphoblastic leukemia; B lymphocytes Author: Oriol de Barrios and Maribel Parra Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Mar 22 10:20:32 2021 CET ModDate: Mon Mar 22 11:01:18 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 18 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1588984 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- UFQOKD+URWPalladioL-Ital Type 1 Custom yes yes no 10 0 CUJOFP+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 VAXIHQ+URWPalladioL-Roma Type 1 Custom yes yes no 19 0 AMNTIP+VnURWPalladioL Type 1 Custom yes yes no 23 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 32 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 35 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 52 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 56 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 60 0 MKNOBG+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 91 0 MKNOBI+PalatinoLinotype TrueType WinAnsi yes yes no 94 0 MKNOCK+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 97 0 GXMHVF+CMSY10 Type 1 Builtin yes yes no 107 0 MKNOBG+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 124 0 MKNOBH+PalatinoLinotype CID TrueType Identity-H yes yes yes 127 0 MKNOBI+PalatinoLinotype TrueType WinAnsi yes yes no 133 0 MKNOCK+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 136 0 LWLIVD+EURM10 Type 1 Builtin yes yes no 163 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-06-29 02:30:14 CEST RepresentationInformation: ijms-22-03127-v2.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-01-31 15:10:21 CET Size: 1588984 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 613 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: Epigenetic Alterations That Affect Gene Expression in BCP-ALL Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Role of Epigenetic Modifications in Cancer Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Histone Methylation Pattern Alterations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Children: Item: Title: Histone 3 Lysine 4 (H3K4) and Lysine 79 (H3K79) Methylation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Histone 3 Lysine 27 (H3K27) Methylation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Histone 3 Lysine 9 (H3K9) and Lysine 36 (H3K36) Methylation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Other Histone Alterations Affecting Methylation Patterns Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: DNA Methylation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Histone acetylation Alterations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Histone Ubiquitination Alterations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Concluding Remarks Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Info: Title: Epigenetic Control of Infant B Cell Precursor Acute Lymphoblastic Leukemia Author: Oriol de Barrios and Maribel Parra Subject: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a highly aggressive malignancy, with poorer prognosis in infants than in adults. A genetic signature has been associated with this outcome but, remarkably, leukemogenesis is commonly triggered by genetic alterations of embryonic origin that involve the deregulation of chromatin remodelers. This review considers in depth how the alteration of epigenetic profiles (at DNA and histone levels) induces an aberrant phenotype in B lymphocyte progenitors by modulating the oncogenic drivers and tumor suppressors involved in key cancer hallmarks. DNA methylation patterns have been widely studied in BCP-ALL and their correlation with survival has been established. However, the effect of methylation on histone residues can be very different. For instance, methyltransferase KMT2A gene participates in chromosomal rearrangements with several partners, imposing an altered pattern of methylated H3K4 and H3K79 residues, enhancing oncogene promoter activation, and conferring a worse outcome on affected infants. In parallel, acetylation processes provide an additional layer of epigenetic regulation and can alter the chromatin conformation, enabling the binding of regulatory factors. Therefore, an integrated knowledge of all epigenetic disorders is essential to understand the molecular basis of BCP-ALL and to identify novel entry points that can be exploited to improve therapeutic options and disease prognosis. 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