PMID- 11122108
OWN - NLM
STAT- MEDLINE
DCOM- 20010215
LR  - 20190705
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 111
IP  - 2
DP  - 2000 Nov
TI  - Interferon alpha in combination with GM-CSF induces the differentiation of 
      leukaemic antigen-presenting cells that have the capacity to stimulate a specific 
      anti-leukaemic cytotoxic T-cell response from patients with chronic myeloid 
      leukaemia.
PG  - 596-607
AB  - Although interferon alpha (IFN-alpha) is able to induce haematological remission 
      in 60-80% of patients with chronic myeloid leukaemia (CML) in early chronic 
      phase, major cytogenetic remissions are only achievable in 30-40%. Recent 
      clinical data suggest that the addition of granulocyte-macrophage 
      colony-stimulating factor (GM-CSF) to IFN-alpha therapy can significantly improve 
      the cytogenetic response in some patients, although the mechanism remains 
      unknown. We hypothesized that the combination of GM-CSF and IFN-alpha induces the 
      differentiation of dendritic cells, which subsequently stimulates a specific 
      anti-leukaemic response. Monocytes from CML patients were cultured in GM-CSF and 
      interleukin (IL)-4 (GM/IL-4)or in GM-CSF and IFN-alpha (GM/IFN-alpha). After 7 d, 
      the number of cells exhibiting typical antigen-presenting cell (APC) morphology 
      was equal in both groups, and fluorescence in situ hybridization (FISH) analysis 
      confirmed that the APCs generated with GM/IFN-alpha were of leukaemic origin. 
      Phenotypically, both sets of APCs expressed typical surface markers; however, 
      CD86, CD83, CD11c, HLA-ABC and HLA-DR expression was significantly higher in the 
      GM/IFN-alpha APCs, whereas CD1a expression was significantly lower. In mixed 
      lymphocyte reactions (MLR), GM/IFN-alpha APCs stimulated the proliferation of 
      allogeneic T cells significantly better than GM/IL-4 APCs. However, both groups 
      of APCs stimulated autologous T-cell proliferation equally. Finally, we assessed 
      the ability of GM/IFN-alpha APCs to induce a leukaemia-specific cytotoxic T-cell 
      response. Some samples generated cytotoxic T lymphocytes (CTLs) that specifically 
      lysed bcr-abl-positive target cells. These data show that the combination of 
      GM-CSF and IFN-alpha, when used in vitro, induces the differentiation of 
      malignant APCs with potent T-cell stimulatory capacity. Although there is no in 
      vivo evidence to support these findings, it is possible that, when administered 
      to CML patients, GM-CSF in combination with IFN-alpha results in the generation 
      of highly stimulatory leukaemic APCs.
FAU - Chen, X
AU  - Chen X
AD  - Klinische Kooperationsgruppe Hamatopoetische Zelltransplantation, Medizinische 
      Klinik III, Klinikum Grosshadern, Universitat Munchen and GSF (National Research 
      Centre for Environment and Health), Munchen, Germany.
FAU - Regn, S
AU  - Regn S
FAU - Raffegerst, S
AU  - Raffegerst S
FAU - Kolb, H J
AU  - Kolb HJ
FAU - Roskrow, M
AU  - Roskrow M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Interferon-alpha)
RN  - 0 (Interleukin-18)
RN  - 207137-56-2 (Interleukin-4)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Antigen-Presenting Cells/*immunology
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Cytotoxicity Tests, Immunologic
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/*therapeutic use
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Interferon-alpha/*therapeutic use
MH  - Interleukin-18/analysis
MH  - Interleukin-4/therapeutic use
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy/*immunology
MH  - *Lymphocyte Activation
MH  - T-Lymphocytes, Cytotoxic/*immunology
EDAT- 2000/12/21 11:00
MHDA- 2001/03/03 10:01
CRDT- 2000/12/21 11:00
PHST- 2000/12/21 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2000/12/21 11:00 [entrez]
AID - bjh2361 [pii]
AID - 10.1046/j.1365-2141.2000.02361.x [doi]
PST - ppublish
SO  - Br J Haematol. 2000 Nov;111(2):596-607. doi: 10.1046/j.1365-2141.2000.02361.x.