title: HA14-1, a small molecule inhibitor of Bcl-2, bypasses chemoresistance in leukaemia cells.
abstract: We analyzed the biological activity of HA14-1, a small organic compound inhibitor of Bcl-2, against established leukaemia cell lines and blasts from acute myeloid leukaemia (AML) patients. HA14-1 had a potent killing activity against the leukaemia cell line that expressed endogenous or ectopic Bcl-2. This activity was mostly caspase-independent and was not altered by the expression of a multidrug-resistant phenotype. Moreover, HA14-1 efficiently induced cell death in a broad spectrum of AML blasts but not in normal peripheral blood lymphocytes. Thus, single-agent regimens using Bcl-2 inhibitors such as HA14-1 may be advantageous in overcoming some forms of chemoresistance in AML.
authors.affiliation: INSERM UMR 601, 9 Quai Moncousu, Nantes F-44000, France. Lisa.Oliver@univ-nantes.fr
authors.forename: Lisa
authors.initials: L
authors.lastname: Oliver
authors.forename: Béatrice
authors.initials: B
authors.lastname: Mahé
authors.forename: René
authors.initials: R
authors.lastname: Gréé
authors.forename: François M
authors.initials: FM
authors.lastname: Vallette
authors.forename: Philippe
authors.initials: P
authors.lastname: Juin
mesh_terms: D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use; D001752:Blast Crisis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D009570:Nitriles / Q000494:pharmacology* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*
chemical_list: D001578:Benzopyrans; D004791:Enzyme Inhibitors; D009570:Nitriles; D019253:Proto-Oncogene Proteins c-bcl-2; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate; D020169:Caspases