Valproic Acid sensitizes CLL cells to apoptosis

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Sorry, repeat post. Andy caught the abstract in November.

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Full article available on www.pubmed.gov

CLL Topics covered Valproic Acid and drugs like it in " Epigenetics " ,

2004.

Mol Bio Jan/Feb 2008

Valproic Acid sensitizes chronic lymphocytic leukemia cells to

apoptosis and restores the balance between pro- and antiapoptotic

proteins.Bokelmann I, Mahlknecht U.

Department of Hematology/Oncology, University of Heidelberg Medical

Center, Im Neuenheimer Feld 410, Heidelberg, Germany.

Chronic lymphocytic leukemia (CLL) is one of the most common

leukemias in adults in the developed world. Despite significant

advances in the treatment of cancer, CLL remains incurable. The main

feature of the disease is the generation of circulating B-cells with

prolonged survival caused by aberrant apoptosis. In this study, we

observe that valproic acid (VPA), a well-established histone

deacetylase (HDAC) inhibitor, mediates apoptosis in CLL cells ex vivo

through caspase activation via both the extrinsic and the intrinsic

apoptosis pathways, as indicated by the activation of the caspase

proteins 8 and 9, and cleavage of the proapoptotic protein BID. The

Bcl-2/Bax ratio was decreased as a consequence of decreased bcl-2

mRNA levels in response to treatment with VPA. With the results

presented in this study, we have identified the HDAC inhibitor VPA as

restoring the apoptotic pathways in CLL cells and thus their ability

to undergo apoptosis.

PMID: 17973028