Related Experiment Video

Updated: May 6, 2026

An Optimized Protocol for Electrophoretic Mobility Shift Assay Using Infrared Fluorescent Dye-labeled Oligonucleotides
09:58

An Optimized Protocol for Electrophoretic Mobility Shift Assay Using Infrared Fluorescent Dye-labeled Oligonucleotides

Published on: November 29, 2016

15.3K

Sox4 is a key oncogenic target in C/EBPα mutant acute myeloid leukemia

Hong Zhang1, Meritxell Alberich-Jorda, Giovanni Amabile

  • 1Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02215, USA; Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

Cancer Cell
|November 5, 2013
PubMed

Insights

Transcription factor C/EBPα inactivation in acute myeloid leukemia (AML) leads to Sox4 overexpression. This contributes to leukemia development by promoting self-renewal and inhibiting differentiation of leukemia-initiating cells (LICs).

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Hematology

Background:

  • Transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) is frequently inactivated in acute myeloid leukemia (AML).
  • Inactivation of C/EBPα leads to a common gene expression profile in AML, but downstream targets driving leukemogenesis remain unclear.

Purpose of the Study:

  • To identify direct downstream targets of C/EBPα in AML.
  • To investigate the role of these targets in regulating leukemia-initiating cell (LIC) phenotype and function.

Main Methods:

  • Gene expression profiling to compare AML models with C/EBPα inactivation and Sox4 overexpression.
  • Functional assays to assess the impact of Sox4 modulation on leukemic cell self-renewal and differentiation.
  • Analysis of leukemia-initiating cells (LICs) from genetically modified murine AML models.

Main Results:

  • Sox4 was identified as a direct transcriptional target of C/EBPα, with inverse correlation between their activities.
  • Downregulation of Sox4 reversed the aberrant self-renewal and restored differentiation in leukemic cells.
  • Gene expression profiles of LICs from Sox4-overexpressing and C/EBPα-mutant AML models showed distinct clustering.

Conclusions:

  • Sox4 overexpression, driven by C/EBPα inactivation, is a key mechanism contributing to AML pathogenesis.
  • Sox4 plays a critical role in conferring a distinct leukemia-initiating cell phenotype in specific AML subtypes.

More Related Videos

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

960
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

7.7K

Related Concept Videos

Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
31.3K
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...
6.1K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.8K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.0K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.2K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

6.1K