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Blood, 15 March 2002, Vol. 99, No. 6, pp. 2248-2251
BRIEF REPORT
Histone deacetylase inhibitor FR901228 enhances adenovirus
infection of hematopoietic cells
Masaki Kitazono,
Vemulkonda
Koneti Rao,
Rob Robey,
Takashi Aikou,
Susan Bates,
Tito Fojo, and
Merrill E. Goldsmith
From the Cancer Therapeutics Branch, Center for Cancer
Research, National Cancer Institute, National Institutes of Health,
Bethesda, MD; and the First Department of Surgery, Faculty of Medicine,
Kagoshima University, Japan
Adenovirus infection of hematopoietic cells frequently
requires high virus concentrations and long incubation times to obtain moderate infection levels because these cells have low levels of
Coxsackie and adenovirus receptor (CAR) and  v integrin.
The effect of treatment with FR901228 (depsipeptide), a histone
deacetylase inhibitor in phase 2 clinical trials, was studied in K562
cells, granulocyte-colony-stimulating factor-mobilized peripheral
blood mononuclear cells (PBMCs), and CD34+ peripheral
blood stem cells (PBSCs). FR901228 increased CAR and v
integrin RNA levels and histone H3 acetylation. FR901228
treatment before adenovirus infection was associated with at least a
10-fold increase in transgene expression from a
 -galactosidase-expressing adenoviral vector. More than 80% of the
PBMCs or CD34+ PBSCs from 7 different donors were
-galactosidase-positive after adenovirus infection with a
multiplicity of infection of 10 for 60 minutes. Increased CAR,
v integrin, and acetylated histone H3 levels were
observed in PBMCs from a patient treated with FR901228. These studies
suggest that FR901228 can increase the efficiency of adenoviral
infection in hematopoietic cells.
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