PMID- 15197237
OWN - NLM
STAT- MEDLINE
DCOM- 20041005
LR  - 20231213
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 76
IP  - 3
DP  - 2004 Sep
TI  - Histone deacetylase inhibition improves dendritic cell differentiation of 
      leukemic blasts with AML1-containing fusion proteins.
PG  - 623-33
AB  - Recurrent cytogenetic abnormalities in leukemic blasts make these an attractive 
      source for dendritic cells (DC) to induce a leukemia-specific immune response. In 
      this study, three leukemic cell lines were investigated: Kasumi-1 and SKNO-1 (two 
      acute myeloid leukemia (AML) cell lines carrying the (8;21)-chromosomal 
      translocation, resulting in the expression of the leukemia-specific fusion 
      protein AML1-eight-twenty-one) and REH, an acute lymphoblastic leukemia cell line 
      with the (12;21)-chromosomal translocation and expression of translocation 
      ETS-like leukemia-AML1. These fusion proteins are implicated in the pathogenesis 
      of the leukemic state by recruiting corepressors and histone deacetylases (HDAC), 
      which interfere with normal cell differentiation. In vitro generation of DC was 
      achieved using a cytokine cocktail containing tumor necrosis factor alpha, 
      granulocyte macrophage-colony stimulating factor, c-kit ligand, and soluble CD40 
      ligand; yet, addition of the HDAC inhibitor (Hdi) trichostatin A enhanced DC 
      differentiation with retention of the fusion transcripts. These leukemic DC 
      showed high-level CD83 and human leukocyte antigen (HLA)-DR expression and had a 
      high allostimulatory potential. Only DC generated from these cell lines after Hdi 
      induced blast-specific cytotoxic T cell responses in HLA-A-matched T cells with a 
      cytotoxicity of 42% in parental Kasumi-1 and 83% in parental REH cells, 
      respectively. This model system suggests that the Hdi supports the in vitro 
      differentiation of DC from leukemic blasts with AML1-containing fusion proteins.
FAU - Moldenhauer, Anja
AU  - Moldenhauer A
AD  - Institute for Transfusion Medicine and Immunehaematology, Campus 
      Virchow-Klinikum, Charite-Universitatsmedizin Berlin, Augustenburger Platz 1, 
      13353 Berlin, Germany. anja.moldenhauer@charite.de
FAU - Frank, Richard C
AU  - Frank RC
FAU - Pinilla-Ibarz, Javier
AU  - Pinilla-Ibarz J
FAU - Holland, Gudrun
AU  - Holland G
FAU - Boccuni, Piernicola
AU  - Boccuni P
FAU - Scheinberg, David A
AU  - Scheinberg DA
FAU - Salama, Abdulgabar
AU  - Salama A
FAU - Seeger, Karl
AU  - Seeger K
FAU - Moore, Malcolm A S
AU  - Moore MA
FAU - Nimer, Stephen D
AU  - Nimer SD
LA  - eng
GR  - CA08748/CA/NCI NIH HHS/United States
GR  - CA70388/CA/NCI NIH HHS/United States
GR  - CA75192/CA/NCI NIH HHS/United States
GR  - DK43025/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040614
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Antigens, CD)
RN  - 0 (Core Binding Factor Alpha 2 Subunit)
RN  - 0 (Cytokines)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Immunoglobulins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RUNX1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 3X2S926L3Z (trichostatin A)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Antigens, CD
MH  - Cell Differentiation/*drug effects/immunology
MH  - Cell Line, Tumor
MH  - Core Binding Factor Alpha 2 Subunit
MH  - Cytokines/pharmacology
MH  - DNA-Binding Proteins/genetics/*immunology/metabolism
MH  - Dendritic Cells/*drug effects/enzymology/immunology
MH  - Enzyme Inhibitors/pharmacology
MH  - HLA-DR Antigens/immunology
MH  - *Histone Deacetylase Inhibitors
MH  - Histone Deacetylases/metabolism
MH  - Humans
MH  - Hydroxamic Acids/pharmacology
MH  - Immunoglobulins/immunology
MH  - Leukemia/*drug therapy/enzymology/immunology
MH  - Lymphocyte Activation/drug effects/immunology
MH  - Lymphocyte Culture Test, Mixed
MH  - Membrane Glycoproteins/immunology
MH  - Oncogene Proteins, Fusion/genetics/*immunology/metabolism
MH  - Proto-Oncogene Proteins/genetics/*immunology/metabolism
MH  - T-Lymphocytes, Cytotoxic/drug effects/immunology
MH  - Transcription Factors/genetics/*immunology/metabolism
MH  - CD83 Antigen
EDAT- 2004/06/16 05:00
MHDA- 2004/10/06 09:00
CRDT- 2004/06/16 05:00
PHST- 2004/06/16 05:00 [pubmed]
PHST- 2004/10/06 09:00 [medline]
PHST- 2004/06/16 05:00 [entrez]
AID - jlb.1103581 [pii]
AID - 10.1189/jlb.1103581 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2004 Sep;76(3):623-33. doi: 10.1189/jlb.1103581. Epub 2004 Jun 14.