Document Detail

Chemotherapy induces bcl-2 cleavage in lymphoid leukemic cell lines.
MedLine Citation:
PMID:  12533044     Owner:  NLM     Status:  MEDLINE    
Bcl-2 is the major anti-apoptotic protein evaluated in studies aimed at understanding programmed cell death. Recent work suggests that the biological activity of Bcl-2 is modulated by proteolytic cleavage, with a 23 kDa cleaved Bcl-2 product having pro-apoptotic activity. In the current study we evaluated the effect of chemotherapy on Bcl-2 cleavage in B lineage leukemic cell lines. JM-1, SUP-B 15 and RS4 leukemic cell lines cleaved Bcl-2 to its 23 kDa form when exposed to the chemotherapeutic agents 1-beta-D-arabinofuranosyl-cytosine (Ara-C) or etoposide (VP-16). Chemotherapy induced Bcl-2 cleavage was blunted by inhibition of caspase activity. Co-culture of leukemic cells with bone marrow stromal cells during chemotherapy exposure resulted in reduced levels of 23 kDa Bcl-2 protein. These observations suggest that the bone marrow microenvironment may contribute to maintenance of residual leukemic disease during treatment by reducing generation of pro-apoptotic 23 kDa Bcl-2.
James E Fortney; Brett M Hall; Lindsay Bartrug; Laura F Gibson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Leukemia & lymphoma     Volume:  43     ISSN:  1042-8194     ISO Abbreviation:  Leuk. Lymphoma     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2003-01-20     Completed Date:  2003-07-09     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  9007422     Medline TA:  Leuk Lymphoma     Country:  England    
Other Details:
Languages:  eng     Pagination:  2171-8     Citation Subset:  IM    
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MeSH Terms
Antineoplastic Agents / pharmacology*
Caspase Inhibitors
Coculture Techniques
Cytarabine / pharmacology
Enzyme Inhibitors / pharmacology
Etoposide / pharmacology
Leukemia, Lymphoid / pathology*
Peptide Hydrolases / metabolism
Proto-Oncogene Proteins c-bcl-2 / drug effects*,  metabolism*
Stromal Cells
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Antineoplastic Agents; 0/Caspase Inhibitors; 0/Enzyme Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 04079A1RDZ/Cytarabine; 6PLQ3CP4P3/Etoposide; EC 3.4.-/Peptide Hydrolases

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