Related Experiment Video

Updated: Jun 26, 2026

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

Epigenetic regulation of microRNAs in acute lymphoblastic leukemia

Jose Roman-Gomez1, Xabier Agirre, Antonio Jiménez-Velasco

  • 1Hematology Department. Reina Sofia Hospital. Avda. Menendez Pidal s/n. 14004 Cordoba. Spain. peperosa@teleline.es

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|January 24, 2009
PubMed
Abstract

Insights

Epigenetic regulation of microRNAs (miRNAs) is altered in acute lymphoblastic leukemia (ALL). Aberrant miRNA methylation in ALL patients significantly impacts disease-free and overall survival, highlighting its prognostic value.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Acute lymphoblastic leukemia (ALL) is a heterogeneous hematologic malignancy.
  • MicroRNAs (miRNAs) play crucial roles in gene regulation and are implicated in various cancers.
  • Epigenetic alterations, including DNA methylation and histone modifications, are increasingly recognized as drivers of leukemogenesis.

Purpose of the Study:

  • To investigate microRNAs (miRNAs) that are epigenetically regulated in acute lymphoblastic leukemia (ALL).
  • To determine the association between miRNA epigenetic modifications and clinical outcomes in ALL patients.

Main Methods:

  • Chromatin immunoprecipitation (ChIP)-on-ChIP was used to assess histone modifications (K4H3me3, K9H3me2) in miRNA 5'UTRs in ALL cell lines.
  • Methylation-specific PCR and quantitative PCR were employed to analyze miRNA methylation status and expression in ALL cell lines and patient samples.
  • The effect of epigenetic drugs (5-Aza-2'-deoxycytidine) on miRNA expression was evaluated.

Main Results:

  • Epigenetic modifications associated with closed chromatin structure were identified in 13 miRNAs.
  • A strong correlation was observed between histone marks, DNA methylation, and miRNA expression in ALL cell lines.
  • Treatment with 5-Aza-2'-deoxycytidine reversed the repressive epigenetic marks and upregulated miRNA expression.
  • Aberrant miRNA methylation was detected in 65% of ALL patients.
  • MiRNA methylation was significantly associated with poorer disease-free survival (DFS) and overall survival (OS) (P < .00001).
  • Multivariate analysis confirmed miRNA methylation profile as an independent prognostic factor for DFS and OS (P < .0001).

Conclusions:

  • Aberrant miRNA methylation is a prevalent epigenetic event in acute lymphoblastic leukemia (ALL).
  • The methylation status of miRNAs serves as a significant independent prognostic biomarker for predicting clinical outcomes in ALL patients.
  • Targeting epigenetic dysregulation of miRNAs may offer potential therapeutic strategies for ALL.

More Related Videos

Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation11:06

Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation

Published on: September 20, 2017

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.