PMID- 17993609
OWN - NLM
STAT- MEDLINE
DCOM- 20080326
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 111
IP  - 3
DP  - 2008 Feb 1
TI  - NKG2D ligand expression in AML increases in response to HDAC inhibitor valproic 
      acid and contributes to allorecognition by NK-cell lines with single KIR-HLA 
      class I specificities.
PG  - 1428-36
AB  - This study exploited alloreactivity of natural killer (NK) cells for augmenting 
      the recognition of human acute myeloid leukemia (AML). To circumvent the 
      inhibitory effect of killer immunoglobulin receptor (KIR) signaling, we generated 
      NK-cell lines with single KIR specificities for major human leukocyte antigen 
      (HLA) class I allotypes. We demonstrated efficient cytolysis of KIR-HLA class 
      I-mismatched primary AML blasts even at low effector-to-target ratios. To define 
      the impact of tumor-associated activating NKG2D-ligands (NKG2D-L), 66 AML 
      patients at diagnosis were analyzed. NKG2D-L were selectively expressed on 
      monoblastic cells in AML M4 and M5 yet absent or weakly expressed on myeloblastic 
      cells in all AML subtypes. Paucity of cell-surface NKG2D-L was not the result of 
      shedding because levels of soluble ULBP1 ligand measured in AML plasma were in 
      the normal range. Notably, purified NKG2D-L(+) monoblastic cells were more 
      susceptible to NK-mediated killing than NKG2D-L(-) myeloblastic cells. 
      Accordingly, induction of cell-surface NKG2D-L by treatment with the histone 
      deacetylase inhibitor, valproic acid, rendered cells more sensitive to NK 
      cytolysis. These data suggest that adoptive transfer of selected populations of 
      alloreactive HLA class I-mismatched NK cells in combination with pharmacologic 
      induction of NKG2D-L merits clinical evaluation as novel approaches to 
      immunotherapy of human AML.
FAU - Diermayr, Stefan
AU  - Diermayr S
AD  - Department of Research, University Hospital Basel, Basel, Switzerland.
FAU - Himmelreich, Heike
AU  - Himmelreich H
FAU - Durovic, Bojana
AU  - Durovic B
FAU - Mathys-Schneeberger, Arina
AU  - Mathys-Schneeberger A
FAU - Siegler, Uwe
AU  - Siegler U
FAU - Langenkamp, Ulrich
AU  - Langenkamp U
FAU - Hofsteenge, Jan
AU  - Hofsteenge J
FAU - Gratwohl, Alois
AU  - Gratwohl A
FAU - Tichelli, Andre
AU  - Tichelli A
FAU - Paluszewska, Monika
AU  - Paluszewska M
FAU - Wiktor-Jedrzejczak, Wieslaw
AU  - Wiktor-Jedrzejczak W
FAU - Kalberer, Christian P
AU  - Kalberer CP
FAU - Wodnar-Filipowicz, Aleksandra
AU  - Wodnar-Filipowicz A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071109
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (KLRK1 protein, human)
RN  - 0 (Ligands)
RN  - 0 (MHC class I-related chain A)
RN  - 0 (Membrane Proteins)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily K)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, Natural Killer Cell)
RN  - 0 (ULBP1 protein, human)
RN  - 0 (valpronic acid)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Cell Line
MH  - Cell Survival
MH  - Cytotoxicity, Immunologic/immunology
MH  - Enzyme Inhibitors/pharmacology
MH  - GPI-Linked Proteins
MH  - HLA Antigens/*immunology
MH  - Histocompatibility Antigens Class I/immunology/metabolism
MH  - *Histone Deacetylase Inhibitors
MH  - Histone Deacetylases/metabolism
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Killer Cells, Natural/*drug effects/*immunology
MH  - Leukemia, Myeloid, Acute/blood/immunology/*metabolism/pathology
MH  - Ligands
MH  - Membrane Proteins/metabolism
MH  - NK Cell Lectin-Like Receptor Subfamily K
MH  - Receptors, Immunologic/*metabolism
MH  - Receptors, Natural Killer Cell
MH  - Sensitivity and Specificity
MH  - Solubility
MH  - Up-Regulation/drug effects
MH  - Valproic Acid/*analogs & derivatives/pharmacology
EDAT- 2007/11/13 09:00
MHDA- 2008/03/28 09:00
CRDT- 2007/11/13 09:00
PHST- 2007/11/13 09:00 [pubmed]
PHST- 2008/03/28 09:00 [medline]
PHST- 2007/11/13 09:00 [entrez]
AID - S0006-4971(20)45397-2 [pii]
AID - 10.1182/blood-2007-07-101311 [doi]
PST - ppublish
SO  - Blood. 2008 Feb 1;111(3):1428-36. doi: 10.1182/blood-2007-07-101311. Epub 2007 
      Nov 9.