INTERNATIONAL CONGRESS OF
CancerGenetics
Epigenetic Alterations in Lymphoid Leukemia: The Role of DNA Methylation, Histone Modifications, and lncRNAs
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Neda Zahmatkesh,1,*
1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
- Introduction: Lymphoid leukemias, including acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL), are heterogeneous hematologic malignancies driven not only by genetic mutations but also by epigenetic dysregulation. Epigenetic mechanisms such as DNA methylation, histone modifications, and long non-coding RNAs (lncRNAs) play crucial roles in leukemogenesis, influencing gene expression without altering DNA sequences. This review aims to highlight the current understanding of these epigenetic alterations and their implications for diagnosis, prognosis, and therapeutic targeting in lymphoid leukemia.
- Methods: A comprehensive literature search was conducted using databases including PubMed, Scopus, and Web of Science. Articles published between 2018 and 2024 were prioritized, with a focus on peer-reviewed research and reviews in English. Keywords such as "DNA methylation", "histone modification", "lncRNA", "epigenetics", and "lymphoid leukemia" were used. Studies investigating both human samples and animal models were included.
- Results: DNA Methylation Aberrant DNA methylation, particularly hypermethylation of tumor suppressor genes, is a hallmark of lymphoid leukemia. In CLL, methylation of DAPK1, CDKN2A, and TP73 has been correlated with poor prognosis and treatment resistance. In ALL, altered methylation of genes such as CDKN1C and FHIT contributes to leukemogenesis and progression. Histone Modifications Histone acetylation and methylation modifications influence chromatin structure and gene transcription. Dysregulation of histone-modifying enzymes, including EZH2, HDACs, and KMT2A, has been observed in both CLL and ALL. For example, overexpression of HDAC1/2 leads to transcriptional repression of differentiation-related genes in ALL, promoting cell proliferation. Long Non-Coding RNAs (lncRNAs) LncRNAs regulate chromatin remodeling and transcription by interacting with epigenetic regulators. Several lncRNAs, such as MALAT1, LINC00152, and NEAT1, are aberrantly expressed in lymphoid leukemias. MALAT1, for example, is upregulated in CLL and modulates the PI3K/AKT signaling pathway, contributing to cell survival. In pediatric ALL, lncRNA MEG3 acts as a tumor suppressor and is often silenced via promoter methylation.
- Conclusion: Epigenetic changes, including DNA methylation, histone modifications, and dysregulation of lncRNAs, are critical contributors to the pathogenesis of lymphoid leukemias. These modifications offer valuable insights into disease mechanisms and represent promising biomarkers for prognosis and therapeutic targets. The integration of epigenetic profiling into routine clinical practice may enhance precision medicine approaches in leukemia treatment.
- Keywords: Lymphoid leukemia, Epigenetics, DNA methylation, Histone modification
