A code of silence in acute myeloid leukemia

The development of acute myeloid leukemia (AML) is associated with a variety of genetic changes. Some of these alterations are epigenetic, wherein the sequence of the genes is unchanged, but chemical modifications to the DNA alter gene expression.

In a study published in the , researchers led by Daniel Tenen at Beth Israel Deaconess Medical Center found that a transcriptional regulator known as C/EBPG was highly expressed in a subset of AML samples that had an epigenetically silenced C/EBPA gene.

By blocking the epigenetic modification of C/EBPA, Tenen and colleagues found that they could reduce C/EBPG and restore normal myeloid .

This study suggests that targeting the balance of C/EBPG and C/EBPA could represent a new therapeutic approach in the treatment of AML.

More information: C/EBPγ deregulation results in differentiation arrest in acute myeloid leukemia. Published in Volume 122, Issue 12 (December 3, 2012)
J Clin Invest. 2012;122(12):4490–4504. doi:10.1172/JCI65102

Abstract
C/EBPs are a family of transcription factors that regulate growth control and differentiation of various tissues. We found that C/EBPγ is highly upregulated in a subset of acute myeloid leukemia (AML) samples characterized by C/EBPα hypermethylation/silencing. Similarly, C/EBPγ was upregulated in murine hematopoietic stem/progenitor cells lacking C/EBPα, as C/EBPα mediates C/EBPγ suppression. Studies in myeloid cells demonstrated that CEBPG overexpression blocked neutrophilic differentiation. Further, downregulation of Cebpg in murine Cebpa-deficient stem/progenitor cells or in human CEBPA-silenced AML samples restored granulocytic differentiation. In addition, treatment of these leukemias with demethylating agents restored the C/EBPα-C/EBPγ balance and upregulated the expression of myeloid differentiation markers. Our results indicate that C/EBPγ mediates the myeloid differentiation arrest induced by C/EBPα deficiency and that targeting the C/EBPα-C/EBPγ axis rescues neutrophilic differentiation in this unique subset of AMLs.

Related Stories

Two-faced leukemia?

date Dec 12, 2011

One kind of leukemia sometimes masquerades as another, according to a study published online this week in the Journal of Experimental Medicine.

A new target in acute myeloid leukemia

date Jul 16, 2012

Acute myeloid leukemia, a common leukemia in adults, is characterized by aberrant proliferation of cancerous bone marrow cells. Activating mutations in a protein receptor known as FLT3 receptor are among the most prevalent ...

Recommended for you

Spicy treatment the answer to aggressive cancer?

date 22 hours ago

It has been treasured by food lovers for thousands of years for its rich golden colour, peppery flavour and mustardy aroma…and now turmeric may also have a role in fighting cancer.

Cancer survivors who smoke perceive less risk from tobacco

date Jul 02, 2015

Cancer survivors who smoke report fewer negative opinions about smoking, have more barriers to quitting, and are around other smokers more often than survivors who had quit before or after their diagnosis, according to a ...

Melanoma mutation rewires cell metabolism

date Jul 02, 2015

A mutation found in most melanomas rewires cancer cells' metabolism, making them dependent on a ketogenesis enzyme, researchers at Winship Cancer Institute of Emory University have discovered.

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.