title: Single-agent Smac-mimetic compounds induce apoptosis in B chronic lymphocytic leukaemia (B-CLL).
abstract: Defective apoptosis is a hallmark of the progression of B chronic lymphocytic leukaemia (B-CLL). Smac-mimetics have been shown to induce apoptosis in several tumours. We describe the in vitro pro-apoptotic activity and regulation of the molecular pathway induced by new Smac-mimetics in B-CLL. The cytotoxic effect was significantly higher in B-CLL samples than in healthy controls. No significant synergistic effect was observed in combined treatment. In conclusion one of our compounds (Smac66), used as monotherapy and not in combination, is highly active against B-CLL cells thus suggesting a promising therapeutic potential as a new class of antileukemic drugs in haematology.
authors.affiliation: Fondazione Matarelli, Dipartimento di Farmacologia Chemioterapia e Tossicologia Medica, Università degli Studi di Milano, Milano, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Scavullo
authors.forename: Federica
authors.initials: F
authors.lastname: Servida
authors.forename: Daniele
authors.initials: D
authors.lastname: Lecis
authors.forename: Francesco
authors.initials: F
authors.lastname: Onida
authors.forename: Carmelo
authors.initials: C
authors.lastname: Drago
authors.forename: Luca
authors.initials: L
authors.lastname: Ferrante
authors.forename: Pierfausto
authors.initials: P
authors.lastname: Seneci
authors.forename: Wilma
authors.initials: W
authors.lastname: Barcellini
authors.forename: Marta
authors.initials: M
authors.lastname: Lionetti
authors.forename: Katia
authors.initials: K
authors.lastname: Todoerti
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
authors.forename: Domenico
authors.initials: D
authors.lastname: Delia
authors.forename: Giorgio Lambertenghi
authors.initials: GL
authors.lastname: Deliliers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D009842:Oligopeptides / Q000494:pharmacology*; D057786:Peptidomimetics / Q000494:pharmacology*; D011379:Prognosis
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D009842:Oligopeptides; D057786:Peptidomimetics; C532637:SMAC peptide