PMID- 19056691
OWN - NLM
STAT- MEDLINE
DCOM- 20090413
LR  - 20210206
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 113
IP  - 11
DP  - 2009 Mar 12
TI  - Regulation of multiple myeloma survival and progression by CD1d.
PG  - 2498-507
LID - 10.1182/blood-2008-06-161281 [doi]
AB  - Down-regulation of conventional human leukocyte antigen (HLA) class I and II 
      molecules from the surface of tumor cells is an important mechanism for tumor 
      immune evasion, survival, and progression. Whether CD1d, a nonconventional, 
      glycolipid-presenting HLA class I-like molecule instructing the function of the 
      immunoregulatory invariant NKT cells can affect tumor cell survival is not known. 
      Here we show that CD1d is highly expressed in premalignant and early myeloma, but 
      with disease progression its expression is reduced and eventually in advanced 
      stages and myeloma cell lines is lost altogether, suggesting that CD1d impacts 
      negatively on myeloma cell survival. Consistent with this, engagement of CD1d by 
      anti-CD1d monoclonal antibodies (mAbs) induces cell death of myeloma cell lines 
      with restored CD1d expression and primary myeloma cells. Cell death induced by 
      monoclonal antibody engagement of CD1d is associated with overexpression of 
      proapoptotic Bax and mitochondrial membrane potential loss but it is 
      caspase-activation independent; in addition, it requires the cytoplasmic tail but 
      not the Tyr residue critical for lysosomal sorting of CD1d. Finally, anti-CD1d 
      cooperates with antimyeloma agents in the killing of myeloma cells. Thus, this 
      work provides evidence linking a novel function of CD1d in the regulation of cell 
      death with tumor survival and progression in humans.
FAU - Spanoudakis, Emmanouil
AU  - Spanoudakis E
AD  - Department of Haematology, Imperial College Healthcare National Health Service 
      (NHS) Trust, Hammersmith and St Mary's Hospital, Imperial College London, London, 
      UK.
FAU - Hu, Ming
AU  - Hu M
FAU - Naresh, Kikkeri
AU  - Naresh K
FAU - Terpos, Evangelos
AU  - Terpos E
FAU - Melo, Valeria
AU  - Melo V
FAU - Reid, Alistair
AU  - Reid A
FAU - Kotsianidis, Ioannis
AU  - Kotsianidis I
FAU - Abdalla, Saad
AU  - Abdalla S
FAU - Rahemtulla, Amin
AU  - Rahemtulla A
FAU - Karadimitris, Anastasios
AU  - Karadimitris A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081203
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD1d)
RN  - 0 (Boronic Acids)
RN  - 0 (CD1D protein, human)
RN  - 0 (Pyrazines)
RN  - 69G8BD63PP (Bortezomib)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Antibodies, Monoclonal/administration & dosage/*pharmacology
MH  - Antigens, CD1d/genetics/immunology/*physiology
MH  - Antineoplastic Combined Chemotherapy Protocols/pharmacology/therapeutic use
MH  - Apoptosis/drug effects
MH  - B-Lymphocytes/drug effects/metabolism
MH  - Boronic Acids/administration & dosage
MH  - Bortezomib
MH  - Cell Aggregation/drug effects
MH  - Cell Survival/drug effects/genetics
MH  - Dexamethasone/administration & dosage
MH  - Disease Progression
MH  - Drug Evaluation, Preclinical
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Multiple Myeloma/drug therapy/*genetics/metabolism/*pathology
MH  - Plasma Cells/drug effects/metabolism
MH  - Pyrazines/administration & dosage
MH  - Tumor Cells, Cultured
EDAT- 2008/12/06 09:00
MHDA- 2009/04/14 09:00
CRDT- 2008/12/06 09:00
PHST- 2008/12/06 09:00 [pubmed]
PHST- 2009/04/14 09:00 [medline]
PHST- 2008/12/06 09:00 [entrez]
AID - S0006-4971(20)37576-5 [pii]
AID - 10.1182/blood-2008-06-161281 [doi]
PST - ppublish
SO  - Blood. 2009 Mar 12;113(11):2498-507. doi: 10.1182/blood-2008-06-161281. Epub 2008 
      Dec 3.