A code of silence in acute myeloid leukemia

November 19, 2012, Journal of Clinical Investigation

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.

Explore further: Two-faced leukemia?

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?

December 12, 2011
One kind of leukemia sometimes masquerades as another, according to a study published online this week in the Journal of Experimental Medicine.

Gene discovery could improve treatment for acute myeloid leukemia

August 13, 2012
Scientists at Albert Einstein College of Medicine of Yeshiva University have made a discovery involving mice and humans that could mean that people with acute myeloid leukemia (AML), a rare and usually fatal cancer, are a ...

A new target in acute myeloid leukemia

July 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 ...

Identifying acute myeloid leukemia gene mutations may indicate risk, best treatment

March 23, 2012
An international group of researchers, including those from Moffitt Cancer Center in Tampa, Fla., have published a paper in the March 14 issue of the New England Journal of Medicine reviewing the results of a study that analyzed ...

Recommended for you

Researchers identify new treatment target for melanoma

January 16, 2018
Researchers in the Perelman School of Medicine at the University of Pennsylvania have identified a new therapeutic target for the treatment of melanoma. For decades, research has associated female sex and a history of previous ...

More evidence of link between severe gum disease and cancer risk

January 16, 2018
Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists ...

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

Pancreatic tumors may require a one-two-three punch

January 15, 2018
One of the many difficult things about pancreatic cancer is that tumors are resistant to most treatments because of their unique density and cell composition. However, in a new Wilmot Cancer Institute study, scientists discovered ...

New immunotherapy approach boosts body's ability to destroy cancer cells

January 12, 2018
Few cancer treatments are generating more excitement these days than immunotherapy—drugs based on the principle that the immune system can be harnessed to detect and kill cancer cells, much in the same way that it goes ...

Cancer's gene-determined 'immune landscape' dictates progression of prostate tumors

January 12, 2018
The field of immunotherapy - the harnessing of patients' own immune systems to fend off cancer - is revolutionizing cancer treatment today. However, clinical trials often show marked improvements in only small subsets of ...

0 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.