Tuesday, November 26, 2013

Two separate studies identify new potential AML treatments

AML, or acute-myeloid leukemia is a cancer characterized by rapid growth of abnormal blood cells. AML is a disease that is actually characterized by a wide range of diversity in terms of genetics. A genetic hallmark of about 10% of AML is mutation of epigenetic repression or C/EBPα. Two separate studies have investigated AML with C/EBPα dysfunction and found two separate potential targets for treatment. Both studies represent the work of international collaborations.

The Armed Forces Institute of Pathology (AFIP)
The first study was published in a recent issue of Cancer Cell in an article entitled: 'Sox4 Is a Key Oncogenic Target in C/EBPα Mutant Acute Myeloid Leukemia'. This article describes how Sox4 expression is normally repressed by C/EBPα but when this regulation is silenced Sox4 is overexpressed leading to leukemic growth. Overexpression of Sox4 independent of C/EBPα silencing led to similar gene expression profiles as those seen when Sox4 overexpression is the result of C/EBPα silencing. Thus Sox4 is a viable target for drug intervention and treatment of AML. The search now begins to find suitable compounds that will inhibit Sox4 function and can therefore be used to treat AML in which C/EBPα dysfunction is seen.

The second study produced an article entitled: 'The gene signature in CCAAT-enhancer-binding protein α dysfunctional acute myeloid leukemia predicts responsiveness to histone deacetylase inhibitors' was published in a recent issue of the journal Haematologica. This study sought a way to reactivate C/EBPα through the use of small molecule inhibitors where they found that histone deacetylase inhibitors had a positive connection. Histone deacetylases (HDAC's) are involved in epigenetic regulation so it is expected that they will be useful in treatments of AML which involves epigenetic repression of C/EBPα.

Structure of the CEBPA protein
by Emw
Both of these studies provide an exciting opportunity to discover new compounds that will be useful in treating AML with C/EBPα dysfunction. The PHERAstar FS is an excellent tool for drug discovery and high throughput screening that will be necessary to discover new compounds that either inhibit Sox4 or inhibit the relevant HDAC's.

Please visit BMG LABTECH's website at: http://www.bmglabtech.com/ to find out more about the PHERAstar FS and other microplate readers that will assist your research.

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