PMID- 11090069
OWN - NLM
STAT- MEDLINE
DCOM- 20010201
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 96
IP  - 12
DP  - 2000 Dec 1
TI  - Up-regulation of costimulatory/adhesion molecules by histone deacetylase 
      inhibitors in acute myeloid leukemia cells.
PG  - 3847-56
AB  - Histone deacetylase inhibitors (HDACIs) have been used to focus on the effects of 
      inducing gene expression through the acetylation of histones which results in 
      chromatin remodeling. The study explored whether HDACIs could induce the 
      expression of costimulatory/adhesion molecules on acute myeloid leukemia (AML) 
      cells, thereby effectively inducing tumor immunity. The expression of CD80, CD86, 
      human leukocyte antigen (HLA)-DR, HLA-ABC, and intracellular adhesion molecule-1 
      (ICAM-1) was tested in human AML cell lines after the addition of HDACI, sodium 
      butyrate (SB). Generally, increased expression of CD86 was observed by SB 
      treatment in a majority of cell lines, and ICAM-1 was expressed in fewer cell 
      lines. Essentially the same results were obtained using other HDACIs such as 
      FR901228, trichostatin A, and trapoxin A. Quantitation of transcripts of CD86 
      accompanied with RNA synthesis inhibition assay and nuclear run-on assay revealed 
      that SB up-regulates the CD86 expression transcriptionally. Furthermore, 
      chromatin immunoprecipitation experiments showed that HDACI treatment caused 
      remarkable acetylation on histone H3 and H4 at CD86 promoter chromatin in vivo. 
      In 30 clinical AML samples, CD86 expression was significantly increased (P <.001) 
      by SB treatment, and the expression of HLA-DR and ICAM-1 was moderately increased 
      (P <.05) by SB treatment. Finally, the allogeneic mixed leukocyte reaction 
      (allo-MLR) against HL60 cells pretreated with SB was enhanced 4-fold compared 
      with allo-MLR obtained with non-treated HL60 cells. These results suggest that 
      the immunotherapeutic use of HDACIs may become a novel tool for treatment of AML. 
      (Blood. 2000;96:3847-3856)
FAU - Maeda, T
AU  - Maeda T
AD  - First Department of Internal Medicine, Nagoya University School of Medicine, 
      Nagoya, Japan.
FAU - Towatari, M
AU  - Towatari M
FAU - Kosugi, H
AU  - Kosugi H
FAU - Saito, H
AU  - Saito H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD)
RN  - 0 (B7-2 Antigen)
RN  - 0 (CD86 protein, human)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chromatin)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Histones)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA, Messenger)
RN  - 107-92-6 (Butyric Acid)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 5688UTC01R (Tretinoin)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Acetylation/drug effects
MH  - Acute Disease
MH  - Antigens, CD/drug effects/genetics/metabolism/*physiology
MH  - B7-2 Antigen
MH  - Butyric Acid/immunology/pharmacology
MH  - Cell Adhesion Molecules/drug effects/*physiology
MH  - Cell Differentiation
MH  - Chromatin
MH  - Enzyme Inhibitors/immunology/pharmacology
MH  - *Histone Deacetylase Inhibitors
MH  - Histones/metabolism
MH  - Humans
MH  - Immunophenotyping
MH  - Intercellular Adhesion Molecule-1/genetics/metabolism
MH  - Interferon-gamma/pharmacology
MH  - Leukemia, Myeloid/immunology/metabolism/*pathology
MH  - Lymphocyte Culture Test, Mixed
MH  - Membrane Glycoproteins/drug effects/genetics/metabolism/*physiology
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/metabolism
MH  - Transcription, Genetic/drug effects
MH  - Tretinoin/pharmacology
MH  - Tumor Cells, Cultured
MH  - Up-Regulation
EDAT- 2000/11/23 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/11/23 11:00
PHST- 2000/11/23 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/23 11:00 [entrez]
AID - S0006-4971(20)48227-8 [pii]
PST - ppublish
SO  - Blood. 2000 Dec 1;96(12):3847-56.