Related Experiment Video

Updated: Feb 4, 2026

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

3.1K

The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation

Natalia Martinez-Soria1, Lynsey McKenzie1, Julia Draper2

  • 1Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, Newcastle University, Brewery Lane, Newcastle upon Tyne NE1 7RU, UK.

Cancer Cell
|October 10, 2018
PubMed

Insights

RUNX1/ETO drives acute myeloid leukemia (AML) by increasing Cyclin D2 (CCND2) expression. Targeting CCND2 with approved drugs halts leukemia cell growth and spread, offering a new therapeutic strategy for AML.

Area of Science:

  • Hematology
  • Molecular Biology
  • Oncology

Background:

  • RUNX1/ETO is a fusion protein driving t(8;21) acute myeloid leukemia (AML).
  • Targeting oncogenic transcription factors in AML presents significant therapeutic challenges.
  • Understanding the transcriptional network is crucial for developing effective AML treatments.

Purpose of the Study:

  • To identify key components of the transcriptional network maintaining t(8;21) AML.
  • To investigate the role of Cyclin D2 (CCND2) in RUNX1/ETO-driven leukemogenesis.
  • To evaluate CCND2 inhibition as a therapeutic strategy for AML.

Main Methods:

  • Utilized epigenomic profiling data and RNA interference (RNAi) screening.
  • Analyzed the cooperation between RUNX1/ETO and AP-1 in regulating CCND2 expression.
  • Assessed the impact of CCND2 knockdown and pharmacological inhibition on AML cells in vitro and in vivo.

Main Results:

  • Identified CCND2 as a critical mediator of RUNX1/ETO-driven leukemic propagation.
  • Demonstrated that RUNX1/ETO and AP-1 cooperate to induce CCND2 expression.
  • Showed that CCND2 inhibition significantly reduces AML cell expansion and engraftment in murine models.

Conclusions:

  • RUNX1/ETO maintains AML by promoting cell cycle progression through CCND2.
  • G1 Cyclin D-CDK complexes are promising therapeutic targets for RUNX1/ETO-driven AML.
  • Pharmacological inhibition of CCND2 offers a viable treatment strategy for this AML subtype.
Keywords:
CCND2CDK6 inhibitionKIT mutationRNAi screenRUNX1/ETOacute myeloid leukemiacell-cycle controlfusion geneimatinibpalbociclib

More Related Videos

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

8.9K
Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells09:16

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

Published on: September 1, 2019

8.0K

Related Concept Videos

Transcription Factors02:16

Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.7K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.8K
Master Transcription Regulators02:23

Master Transcription Regulators

2.8K
Transcription Elongation Factors02:35

Transcription Elongation Factors

Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
13.9K
Transcription Elongation Factors02:35

Transcription Elongation Factors

4.8K
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
7.4K