Document Detail


Methods for the analysis of histone H3 and H4 acetylation in blood.
MedLine Citation:
PMID:  22772164     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
LBH589 is one of the many histone deacetylase inhibitors (HDACi) that are currently in clinical trial. Despite their wide-spread use, there is little literature available describing the typical levels of histone acetylation in untreated peripheral blood, the treatment and storage of samples to retain optimal measurement of histone acetylation nor methods by which histone acetylation analysis may be monitored and measured during the course of a patient's treatment. In this study, we have used cord or peripheral blood as a source of human leukocytes, performed a comparative analysis of sample processing methods and developed a flow cytometric method suitable for monitoring histone acetylation in isolated lymphocytes and liquid tumors. Western blotting and immunohistochemistry techniques have also been addressed. We have tested these methods on blood samples collected from four patients treated with LBH589 as part of an Australian Children's Cancer Clinical Trial (CLBH589AAU03T) and show comparable results when comparing in vitro and in vivo data. This paper does not seek to correlate histone acetylation levels in peripheral blood with clinical outcome but describes methods of analysis that will be of interest to clinicians and scientists monitoring the effects of HDACi on histone acetylation in blood samples in clinical trials or in related research studies.
Authors:
Lin Rigby; Andrea Muscat; David Ashley; Elizabeth Algar
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-09
Journal Detail:
Title:  Epigenetics : official journal of the DNA Methylation Society     Volume:  7     ISSN:  1559-2308     ISO Abbreviation:  Epigenetics     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-28     Completed Date:  2013-01-14     Revised Date:  2013-08-12    
Medline Journal Info:
Nlm Unique ID:  101265293     Medline TA:  Epigenetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  875-82     Citation Subset:  IM    
Affiliation:
Molecular Oncology Laboratory, Murdoch Children's Research Institute, Parkville, Australia.
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MeSH Terms
Descriptor/Qualifier:
Acetylation / drug effects
Adolescent
Child
Flow Cytometry / methods*
Histone Acetyltransferases / metabolism*
Histone Deacetylase Inhibitors / pharmacology*
Histones / blood*,  metabolism
Humans
Hydroxamic Acids / pharmacology
Indoles / pharmacology
Leukemia / blood,  metabolism
Lymphocytes / metabolism
Chemical
Reg. No./Substance:
0/Histone Deacetylase Inhibitors; 0/Histones; 0/Hydroxamic Acids; 0/Indoles; 0/panobinostat; EC 2.3.1.48/Histone Acetyltransferases
Comments/Corrections

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