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Updated: May 18, 2026

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
09:16

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells

Published on: September 1, 2019

Acute myeloid leukemia with translocation (8;16)(p11;p13) and MYST3-CREBBP rearrangement harbors a distinctive

M Díaz-Beyá1, A Navarro, G Ferrer

  • 1Department of Hematology, Hospital Clínic, University of Barcelona, Barcelona, Spain.

Leukemia
|October 2, 2012
PubMed

Insights

Acute myeloid leukemia with t(8;16) has a unique microRNA signature, with many downregulated microRNAs. This epigenetic regulation partially targets the RET proto-oncogene.

Area of Science:

  • Hematology
  • Molecular Biology
  • Epigenetics

Background:

  • Acute myeloid leukemia (AML) with the t(8;16) chromosomal translocation presents unique clinical and biological features.
  • The specific microRNA expression profile in t(8;16) AML remains largely uncharacterized.

Purpose of the Study:

  • To identify the distinct microRNA signature in t(8;16) AML.
  • To investigate the epigenetic regulation of these microRNAs and their potential targets.

Main Methods:

  • MicroRNA profiling of 7 t(8;16) AML patients and 113 other AML subtypes using hierarchical and supervised cluster analysis.
  • Analysis of mRNA expression for STAT3 and c-Myc, bioinformatic analysis for methylation-regulated microRNAs, and in vitro epigenetic modulation using 5-aza-2'-deoxycytidine and trichostatin A.
  • Cross-correlation of mRNA and microRNA expression, followed by functional validation using Renilla-luciferase assays and flow cytometry to confirm RET proto-oncogene regulation.

Main Results:

  • t(8;16) AML patients exhibited a distinct microRNA signature, clustering independently.
  • A signature of 94 microRNAs was identified, predominantly downregulated, including miR-21 and the miR-17-92 cluster, with significant STAT3 downregulation.
  • Epigenetic analysis revealed that 27 of 29 potentially methylation-regulated microRNAs were re-expressed after treatment with epigenetic modifiers, and RET proto-oncogene was confirmed as a target regulated by specific microRNAs (miR-218, miR-128, miR-27b, miR-15a, miR-195).

Conclusions:

  • t(8;16) AML possesses a specific microRNA signature that is partly regulated by epigenetic mechanisms.
  • The RET proto-oncogene is a key target of this microRNA signature in t(8;16) AML.

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