PMID- 9365828
OWN - NLM
STAT- MEDLINE
DCOM- 19980108
LR  - 20191024
IS  - 1045-2257 (Print)
IS  - 1045-2257 (Linking)
VI  - 20
IP  - 3
DP  - 1997 Nov
TI  - Dendritic cells generated from blood precursors of chronic myelogenous leukemia 
      patients carry the Philadelphia translocation and can induce a CML-specific 
      primary cytotoxic T-cell response.
PG  - 215-23
AB  - Dendritic cells (DC) are professional antigen-presenting cells specialized in the 
      initiation of primary immune responses. We were interested to know whether mature 
      DC can be grown in vitro from peripheral blood mononuclear cells (PBMC) of 
      patients with chronic myelogenous leukemia (CML), and whether they carry the 
      Philadelphia (Ph) translocation. Using a method recently described, DC were 
      generated from PBMC precursors of 12 patients with CML using GM-CSF, IL-4, and 
      monocyte-conditioned medium. DC exhibited the typical morphology with thin 
      cytoplasmatic processes and expressed high levels of MHC class II, CD86, and CD83 
      typical for mature DC. After sorting with the monoclonal antibody CD83, a cell 
      population of more than 95% CD83 positive cells was obtained. The presence of the 
      Ph translocation was analyzed in these cells, in PBMC, lymphoblastoid cell lines 
      (LCL), and in phytohemagglutinin (PHA)-induced T blasts from the same patients by 
      fluorescence in situ hybridization (FISH). In contrast to all other cells 
      analyzed, the vast majority of DC (95.9 +/- 0.7%) displayed the Ph translocation, 
      irrespective of disease stage or therapy. PBMC were predominantly positive for 
      the Ph chromosome (67.6 +/- 7.3%), whereas only 11.4 +/- 1% of the B cells and 
      4.4 +/- 1.1% of the PHA blasts carried the Ph translocation. Using such leukemic 
      DC as antigen-presenting cells, a primary CML-directed cytotoxic immune response 
      in vitro was obtained, as shown by the specific recognition of Ph chromosome 
      positive cells. We conclude that DC can be generated from blood progenitors of 
      CML patients in vitro and exhibit, to a large extent, the Ph translocation. Such 
      DC, which in a preliminary experiment have been able to induce a primary 
      CML-directed cytotoxic immune response in vitro, might be ideal candidates for 
      adoptive immunotherapy either by direct transfer of DC for in vivo generation of 
      a T-cell response or by in vitro generation of CML-specific cytotoxic autologous 
      or HLA-matched normal T-cell clones for use in vivo.
FAU - Eibl, B
AU  - Eibl B
AD  - Department of Internal Medicine, University of Innsbruck, Austria.
FAU - Ebner, S
AU  - Ebner S
FAU - Duba, C
AU  - Duba C
FAU - Bock, G
AU  - Bock G
FAU - Romani, N
AU  - Romani N
FAU - Erdel, M
AU  - Erdel M
FAU - Gachter, A
AU  - Gachter A
FAU - Niederwieser, D
AU  - Niederwieser D
FAU - Schuler, G
AU  - Schuler G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Genes Chromosomes Cancer
JT  - Genes, chromosomes & cancer
JID - 9007329
SB  - IM
MH  - Cell Line, Transformed/chemistry
MH  - Cells, Cultured
MH  - Clone Cells
MH  - Cytotoxicity Tests, Immunologic
MH  - Cytotoxicity, Immunologic
MH  - Dendritic Cells/chemistry/*physiology
MH  - Flow Cytometry
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics/*immunology/pathology
MH  - Leukocytes, Mononuclear/chemistry
MH  - Lymphocyte Activation/genetics
MH  - *Philadelphia Chromosome
MH  - T-Lymphocytes, Cytotoxic/chemistry/immunology/*physiology
EDAT- 1997/11/20 07:04
MHDA- 2000/06/20 09:00
CRDT- 1997/11/20 07:04
PHST- 1997/11/20 07:04 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1997/11/20 07:04 [entrez]
AID - 10.1002/(SICI)1098-2264(199711)20:3<215::AID-GCC1>3.0.CO;2-5 [pii]
AID - 10.1002/(sici)1098-2264(199711)20:3<215::aid-gcc1>3.0.co;2-5 [doi]
PST - ppublish
SO  - Genes Chromosomes Cancer. 1997 Nov;20(3):215-23. doi: 
      10.1002/(sici)1098-2264(199711)20:3<215::aid-gcc1>3.0.co;2-5.