PMID- 15805294
OWN - NLM
STAT- MEDLINE
DCOM- 20050526
LR  - 20220316
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 65
IP  - 7
DP  - 2005 Apr 1
TI  - Altered IFNgamma signaling and preserved susceptibility to activated natural 
      killer cell-mediated lysis of BCR/ABL targets.
PG  - 2914-20
AB  - Previous studies have shown that BCR/ABL oncogene, the molecular counterpart of 
      the Ph1 chromosome, could represent a privileged target to natural killer (NK) 
      cells. In the present study, we showed that activated peripheral NK cells killed 
      high-level BCR/ABL transfectant UT-7/9 derived from the pluripotent hematopoietic 
      cell line UT-7 with a high efficiency. To further define the mechanisms 
      controlling BCR/ABL target susceptibility to NK-mediated lysis, we studied the 
      effect of IFNgamma, a key cytokine secreted by activated NK cells, on the lysis 
      of these targets. Treatment of UT-7, UT-7/neo, and low BCR/ABL transfectant 
      UT-7/E8 cells with IFNgamma resulted in a dramatic induction of human leukocyte 
      antigen class I (HLA-I) molecules and subsequently in their reduced 
      susceptibility to NK-mediated cytolysis likely as a consequence of inhibitory NK 
      receptors engagement. In contrast, such treatment neither affected HLA-I 
      expression on transfectants expressing high level of BCR/ABL (UT-7/9) nor 
      modulated their lysis by NK cells. Our data further show that the high-level 
      BCR/ABL in UT-7/9 cells display an altered IFNgamma signaling, as evidenced by a 
      decrease in IFN regulatory factor-1 (IRF-1) and signal transducers and activators 
      of transcription (STAT) 1 induction and activation in response to IFNgamma, 
      whereas this pathway is normal in UT-7 and UT-7/E8 cells. A decreased HLA-I 
      induction and nuclear phospho-STAT1 nuclear translocation were also observed in 
      blasts from most chronic myelogenous leukemia patients in response to IFNgamma. 
      These results outline the crucial role of IFNgamma in the control of target cell 
      susceptibility to lysis by activated NK cells and indicate that the altered 
      response to IFNgamma in BCR/ABL targets may preserve these cells from the 
      cytokine-induced negative regulatory effect on their susceptibility to 
      NK-mediated lysis.
FAU - Cebo, Christelle
AU  - Cebo C
AD  - Institut National de la Sante et de la Recherche Medicale U487, Villejuif, 
      France.
FAU - Voutsadakis, Ioannis A
AU  - Voutsadakis IA
FAU - Da Rocha, Sylvie
AU  - Da Rocha S
FAU - Bourhis, Jean-Henri
AU  - Bourhis JH
FAU - Jalil, Abdelali
AU  - Jalil A
FAU - Azzarone, Bruno
AU  - Azzarone B
FAU - Turhan, Ali G
AU  - Turhan AG
FAU - Chelbi-Alix, Mounira
AU  - Chelbi-Alix M
FAU - Chouaib, Salem
AU  - Chouaib S
FAU - Caignard, Anne
AU  - Caignard A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Benzamides)
RN  - 0 (HLA Antigens)
RN  - 0 (Interferon-alpha)
RN  - 0 (Piperazines)
RN  - 0 (Pyrimidines)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
MH  - Benzamides
MH  - Cell Nucleus/metabolism
MH  - Fusion Proteins, bcr-abl/biosynthesis/genetics/*immunology
MH  - HLA Antigens/immunology
MH  - Hematopoietic Stem Cells/cytology/*immunology/physiology
MH  - Humans
MH  - Imatinib Mesylate
MH  - Immunotherapy, Adoptive
MH  - Interferon-alpha/pharmacology
MH  - Interferon-gamma/*immunology
MH  - Killer Cells, Natural/*immunology
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL 
      Positive/blood/immunology/metabolism/therapy
MH  - Piperazines/pharmacology
MH  - Pyrimidines/pharmacology
MH  - Signal Transduction
MH  - Transfection
EDAT- 2005/04/05 09:00
MHDA- 2005/05/27 09:00
CRDT- 2005/04/05 09:00
PHST- 2005/04/05 09:00 [pubmed]
PHST- 2005/05/27 09:00 [medline]
PHST- 2005/04/05 09:00 [entrez]
AID - 65/7/2914 [pii]
AID - 10.1158/0008-5472.CAN-04-1932 [doi]
PST - ppublish
SO  - Cancer Res. 2005 Apr 1;65(7):2914-20. doi: 10.1158/0008-5472.CAN-04-1932.