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.

add to favorites email to friend print save as pdf

Related Stories

Two-faced leukemia?

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

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

Discovery could lead to new cancer treatment

17 hours ago

A team of scientists from the University of Colorado School of Medicine has reported the breakthrough discovery of a process to expand production of stem cells used to treat cancer patients. These findings could have implications ...

Is the HPV vaccine necessary?

23 hours ago

As the school year starts in full swing many parents wonder if their child should receive the HPV vaccine, which is recommended for girls ages 11-26 and boys 11-21. There are a lot of questions and controversy around this ...

User comments