Journal Article

Disease-specific epigenetic deregulation of enhancers, transposons, and polycomb targets in acute promyelocytic leukemia

Lehmann, Sören, Bengtzén, Sofia, Ekwall, Karl, Zhong, Xiangfu, Gamboa-Cedeno, Angelica, Lennartsson, Andreas, Cordeddu, Lina

2025

Overview

Background Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML), characterized by a fusion between the PML and RARA genes and by a block in the myeloid maturation at the promyelocytic stage. Methods This study investigates the epigenetic landscape of APL by integrating ChIP-seq data on eight histone modifications and RNA-seq in APL as well as non-APL AML. APL showed a distinct chromatin profile that differed from non-APL AML. Results We describe APL-specific changes in H3K27ac, H3K9me3, and H3K27me3 with impact on enhancer activity, repression of transposable elements, and Polycomb regulated gene repression. The APL-specific H3K27ac pattern identifies APL-specific enhancer and super-enhancer regions, including a subset of enhancers that are bound by the PML-RARA fusion protein. While chromatin bound specifically by PML-RARA were dominantly active, APL was also characterized by gain of APL-specific heterochromatin states with significant gains of H3K9me3 enriched lamina-associated domains and the transposable elements LINE, LTR, and SINE. Conclusion These findings suggest a unique enhancer and heterochromatin profile in APL, with implications for transcription regulation and treatment response. These findings offer novel insights into the pathogenesis of APL.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Acute myeloid leukemia / Acute promyelocytic leukemia / Acute promyeloid leukemia / Annotations / Anopheles / Bioinformatics / Biomedical and Life Sciences / Biomedicine / Bone marrow / Cancer Research / Chromatin / Chromatin - metabolism / Chromatin state / Chromosomes / Data processing / Diseases / DNA Transposable Elements / Enhancer Elements, Genetic / Enhancers / Epigenesis, Genetic / Epigenetic inheritance / Epigenetics / Fusion protein / Gene expression / Gene Expression Regulation, Leukemic / Gene regulation / Genes / Genomes / Genomics / Heterochromatin / Histones / Histones - metabolism / Human Genetics / Humans / Leukemia / Leukemia, Promyelocytic, Acute - genetics / Leukemia, Promyelocytic, Acute - metabolism / Long interspersed nucleotide elements / Medicine/Public Health / Metabolomics / Oncogene Proteins, Fusion - genetics / Oncogene Proteins, Fusion - metabolism / Patients / Polycomb group proteins / Polycomb-Group Proteins - genetics / Polycomb-Group Proteins - metabolism / Promyeloid leukemia / Protein binding / Quality control / RNA / Short interspersed nucleotide elements / Software / Systems Biology / Transposons