title: Inhibition of Bcl-xL expression sensitizes T-cell acute lymphoblastic leukemia cells to chemotherapeutic drugs.
abstract: We have examined the effects of antisense oligonucleotides to bcl-x on the survival and chemosensitivity of CEM cells, a T-acute lymphoblastic leukemia (T-ALL) cell line. Also, we have measured the levels of Bcl-2, Bcl-x, and Bax in 20 cases of T-ALL. By 18 h after the bcl-x antisense treatment, CEM cells showed over a 75% reduction in the levels of Bcl-xL protein and over 30% decreased viable cell counts compared with cells treated with the control oligonucleotide. The combination of bcl-x antisense plus either dexamethasone or doxorubicin showed either strong synergistic or additive killing of CEM cells, respectively. These findings indicate that bcl-x antisense has cytotoxic activity and increases chemotherapy-induced cell death in CEM cells, a model for T-ALL.
authors.affiliation: University of California, San Diego Medical Center, 200 West Arbor Drive, Mail Code 8320, San Diego, CA 92103, USA. ebroome@ucsd.edu
authors.forename: H Elizabeth
authors.initials: HE
authors.lastname: Broome
authors.forename: Alice L
authors.initials: AL
authors.lastname: Yu
authors.forename: Mitch
authors.initials: M
authors.lastname: Diccianni
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Camitta
authors.forename: Brett P
authors.initials: BP
authors.lastname: Monia
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Dean
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004317:Doxorubicin / Q000633:toxicity*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D020319:Oligodeoxyribonucleotides, Antisense / Q000633:toxicity*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics*; D012008:Recurrence; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D020319:Oligodeoxyribonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D003907:Dexamethasone; D004317:Doxorubicin