title: Chemotherapy induces bcl-2 cleavage in lymphoid leukemic cell lines.
abstract: 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.
authors.affiliation: Department of Pediatrics, P.O. Box 9214, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Fortney
authors.forename: Brett M
authors.initials: BM
authors.lastname: Hall
authors.forename: Lindsay
authors.initials: L
authors.lastname: Bartrug
authors.forename: Laura F
authors.initials: LF
authors.lastname: Gibson
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D061945:Caspase Inhibitors; D018920:Coculture Techniques; D003561:Cytarabine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D007945:Leukemia, Lymphoid / Q000473:pathology*; D010447:Peptide Hydrolases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects* / Q000378:metabolism*; D017154:Stromal Cells; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D003561:Cytarabine; D005047:Etoposide; D010447:Peptide Hydrolases