PMID- 11122143
OWN - NLM
STAT- MEDLINE
DCOM- 20010215
LR  - 20171116
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 111
IP  - 3
DP  - 2000 Dec
TI  - Impaired expression of the CD3-zeta chain in peripheral blood T cells of patients 
      with chronic myeloid leukaemia results in an increased susceptibility to 
      apoptosis.
PG  - 817-25
AB  - In patients with myeloid malignancies, cell-mediated immunity is often 
      suppressed, being most profound in those with advanced disease. Such immune 
      dysfunction, as demonstrated in many patients with chronic lymphocytic leukaemia 
      (CLL) and myelodysplastic syndrome (MDS), may, at least in part, be due to 
      altered expression of the CD3-zeta chain, which is an important component of the 
      T-cell receptor (TCR). We speculated that impaired expression of the TCR-zeta 
      chain would be evident in peripheral blood T cells of patients with chronic 
      myeloid leukaemia (CML) and that such an abnormality would result in an increased 
      ex vivo susceptibility to apoptosis. In this study, we demonstrated that, 
      compared with normal controls, zeta chain expression was significantly 
      downregulated in all of the T-cell subsets (P < 0.009) in more than 90% of CML 
      patients. In addition, there was a significantly lower expression of the 
      CD3-epsilon chain (P < 0.001) in patients than in controls. In those patients 
      with abnormal zeta chain expression, the proportion of lymphocytes with 
      spontaneous DNA fragmentation, as determined by terminal deoxynucleotide 
      transferase-mediated dUTP-biotin nick-end labelling (TUNEL) assays, was also 
      significantly higher (P < 0.002) than controls. From all of the patients tested, 
      it was possible to upregulate partially zeta chain expression and hence to reduce 
      the susceptibility to apoptosis by cross-linking the T cells with interleukin 
      (IL)-2, interferon (IFN)-alpha or immobilized CD3. In addition, such cross-linked 
      T cells showed a significantly higher capacity to proliferate than the native CML 
      T cells.
FAU - Chen, X
AU  - Chen X
AD  - Klinische Kooperationsgruppe Hamatopoetische Zelltransplantation, Medizinische 
      Klinik III, Klinikum Grosshadern, Ludwigs-Maximilians-Universitat, Munchen, 
      Germany.
FAU - Woiciechowsky, A
AU  - Woiciechowsky A
FAU - Raffegerst, S
AU  - Raffegerst S
FAU - Schendel, D
AU  - Schendel D
FAU - Kolb, H J
AU  - Kolb HJ
FAU - Roskrow, M
AU  - Roskrow M
LA  - eng
PT  - Journal Article
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (CD3 Complex)
RN  - 0 (CD56 Antigen)
RN  - 0 (Cross-Linking Reagents)
RN  - 0 (Immunoglobulin epsilon-Chains)
RN  - 0 (Interferon-alpha)
RN  - 0 (Interleukin-2)
RN  - 0 (Receptor-CD3 Complex, Antigen, T-Cell)
SB  - IM
MH  - Adult
MH  - *Apoptosis/drug effects
MH  - CD3 Complex/immunology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD56 Antigen/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cell Division/drug effects
MH  - Cross-Linking Reagents/pharmacology
MH  - Flow Cytometry
MH  - Gene Expression/drug effects
MH  - *Gene Rearrangement, T-Lymphocyte
MH  - Humans
MH  - Immunoglobulin epsilon-Chains/genetics
MH  - In Situ Nick-End Labeling
MH  - Interferon-alpha/pharmacology
MH  - Interleukin-2/pharmacology
MH  - Killer Cells, Natural/immunology
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics/immunology
MH  - Middle Aged
MH  - Receptor-CD3 Complex, Antigen, T-Cell/*genetics
MH  - T-Lymphocytes/*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 - bjh2415 [pii]
PST - ppublish
SO  - Br J Haematol. 2000 Dec;111(3):817-25.