Document Detail

Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-x(L) is an essential survival protein of human myeloma cells.
MedLine Citation:
PMID:  12070027     Owner:  NLM     Status:  MEDLINE    
Multiple myeloma (MM) is a plasma cell malignancy that occurs mainly in bone marrow. As MM cells proliferate slowly, it would seem essential to find means of preventing their growth and accumulation inside bone marrow. The present study used an antisense strategy to elucidate the respective roles of Bcl-2, Bcl-x(L), and Mcl-1 proteins in myeloma cell survival. Each antisense oligonucleotide (ASO; Bcl-2, Bcl-x(L), or Mcl-1 ASO) introduced into human myeloma cell lines by electroporation induced a marked reduction in the level of the corresponding protein. Mcl-1 ASO triggers an important decrease of viability in all myeloma cell lines tested and in 2 primary myeloma cells, whereas neither Bcl-2 nor Bcl-x(L) ASO affected the viability of myeloma cells. The decrease of cell viability induced by Mcl-1 ASO treatment was associated with an induction of apoptosis that occurred through the disruption of mitochondrial membrane potential Delta Psi m and the activation of executioner caspase-3. Furthermore, we have shown that interleukin 6 cannot prevent the Mcl-1 ASO-induced apoptosis. Finally, although Bcl-2 ASO treatment alone has no effect, it can sensitize myeloma cell lines to dexamethasone (Dex), whereas Bcl-x(L) ASO in combination with Dex still had no effect. As MM remains an incurable disease despite intensive chemotherapy, these results suggest that Mcl-1 antisense strategy rather than Bcl-2 antisense strategy could be of considerable importance in the treatment of MM.
Sophie Derenne; Brett Monia; Nicholas M Dean; Jennifer K Taylor; Marie-Josée Rapp; Jean-Luc Harousseau; Régis Bataille; Martine Amiot
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Blood     Volume:  100     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-06-18     Completed Date:  2002-07-26     Revised Date:  2008-07-09    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  194-9     Citation Subset:  AIM; IM    
Institut National de la Santé et de la Recherche Médicale Unité 463 Institut de Biologie, Nantes, France.
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MeSH Terms
Apoptosis / drug effects
Cell Survival / drug effects
Interleukin-6 / pharmacology
Middle Aged
Multiple Myeloma / pathology
Neoplasm Proteins / antagonists & inhibitors,  physiology
Oligonucleotides, Antisense / pharmacology*
Plasmacytoma / pathology*
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors,  physiology*
Tumor Cells, Cultured
bcl-X Protein
Reg. No./Substance:
0/BCL2L1 protein, human; 0/Interleukin-6; 0/Neoplasm Proteins; 0/Oligonucleotides, Antisense; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-X Protein; 0/myeloid cell leukemia sequence 1 protein

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