PMID- 12764370
OWN - NLM
STAT- MEDLINE
DCOM- 20030708
LR  - 20220228
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 17
IP  - 6
DP  - 2003 Jun
TI  - Expression of CD1d by myelomonocytic leukemias provides a target for cytotoxic 
      NKT cells.
PG  - 1068-77
AB  - Natural killer T (NKT) cells with an invariant T-cell receptor for 
      alpha-galactosylceramide (alphaGalCer) that is presented by CD1d have been 
      reported to be cytotoxic for myelomonocytic leukemia cells. However, the 
      necessity for leukemia cell CD1d expression, the role of alphaGalCer, and the 
      cytotoxic mechanisms have not been fully elucidated. We evaluated these issues 
      with myeloid leukemia cells from 14 patients and purified NKT cells that were 
      alphaGalCer/CD1d reactive. CD1d was expressed by 80-100% of cells in three of 
      seven acute myeloid leukemias (AMLs) and by 28-77% of cells in five of six 
      juvenile myelomonocytic leukemias (JMML). CD1d+ AML cells were myelomonocytic or 
      monoblastic types, and CD1d+ JMML cells were differentiated and CD34-. 
      Cytotoxicity required leukemia cell CD1d expression and was increased by 
      alphaGalCer (P<0.0001) and inhibited by anti-CD1d mAb (P<0.001). The 
      perforin/granzyme-B pathway of NKT cells caused up to 85% of cytotoxicity, and 
      TNF-alpha, FASL, and TRAIL mediated additional killing. CD56+ NKT cells expressed 
      greater perforin and were more cytotoxic than CD56 NKT cells without alphaGalCer 
      (P<0.0001), but both subpopulations were highly and equally cytotoxic in the 
      presence of alphaGalCer. We conclude that CD1d expression is stage-specific for 
      myelomonocytic leukemias and could provide a target for NKT-cell-mediated 
      immunotherapy.
FAU - Metelitsa, L S
AU  - Metelitsa LS
AD  - Division of Hematology-Oncology, Department of Pediatrics, Children's Hospital 
      Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA 90027, USA.
FAU - Weinberg, K I
AU  - Weinberg KI
FAU - Emanuel, P D
AU  - Emanuel PD
FAU - Seeger, R C
AU  - Seeger RC
LA  - eng
GR  - CA 22794/CA/NCI NIH HHS/United States
GR  - CA 59318/CA/NCI NIH HHS/United States
GR  - CA 80916/CA/NCI NIH HHS/United States
GR  - CA 81403/CA/NCI NIH HHS/United States
GR  - HL 54850/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antigens, CD1)
RN  - 0 (Antigens, CD1d)
RN  - 0 (CD1D protein, human)
RN  - 0 (CD56 Antigen)
RN  - 0 (Galactosylceramides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Pore Forming Cytotoxic Proteins)
RN  - 126465-35-8 (Perforin)
RN  - EC 3.4.21.- (GZMB protein, human)
RN  - EC 3.4.21.- (Granzymes)
RN  - EC 3.4.21.- (Serine Endopeptidases)
SB  - IM
MH  - Antigens, CD1/*metabolism
MH  - Antigens, CD1d
MH  - Bone Marrow/pathology
MH  - CD56 Antigen/metabolism
MH  - Case-Control Studies
MH  - Cells, Cultured
MH  - Cytotoxicity, Immunologic/drug effects
MH  - Galactosylceramides/*pharmacology
MH  - Gene Expression Profiling
MH  - Granzymes
MH  - Humans
MH  - Immunophenotyping
MH  - Killer Cells, Natural/*immunology
MH  - Leukemia, Myelomonocytic, Acute/*metabolism/pathology
MH  - Membrane Glycoproteins/metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Perforin
MH  - Pore Forming Cytotoxic Proteins
MH  - Serine Endopeptidases/metabolism
MH  - Signal Transduction
MH  - T-Lymphocytes, Cytotoxic/*immunology
EDAT- 2003/05/24 05:00
MHDA- 2003/07/09 05:00
CRDT- 2003/05/24 05:00
PHST- 2003/05/24 05:00 [pubmed]
PHST- 2003/07/09 05:00 [medline]
PHST- 2003/05/24 05:00 [entrez]
AID - 2402943 [pii]
AID - 10.1038/sj.leu.2402943 [doi]
PST - ppublish
SO  - Leukemia. 2003 Jun;17(6):1068-77. doi: 10.1038/sj.leu.2402943.