Journal article
BMS-214662 induces mitochondrial apoptosis in chronic myeloid leukemia (CML) stem/progenitor cells, including CD34+38− cells, through activation of protein kinase Cβ
Abstract
Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder maintained by cancer stem cells. To target this population, we investigated the mechanism of action of BMS-214662, developed as a farnesyl transferase inhibitor (FTI) and unique in inducing apoptosis in these cells. By contrast, a related congener and equally effective FTI, BMS-225975 does not induce apoptosis, indicating a novel mechanism of action. BMS-214662 significantly …
Authors
Pellicano F; Copland M; Jorgensen HG; Mountford J; Leber B; Holyoake TL
Journal
Blood, Vol. 114, No. 19, pp. 4186–4196
Publisher
American Society of Hematology
Publication Date
November 5, 2009
DOI
10.1182/blood-2009-05-219550
ISSN
0006-4971
Associated Experts
Fields of Research (FoR)
Medical Subject Headings (MeSH)
ADP-ribosyl Cyclase 1Antigens, CD34ApoptosisBenzodiazepinesBryostatinsCaspasesCyclin ACyclin-Dependent Kinase 2E2F1 Transcription FactorEnzyme ActivationEnzyme InhibitorsFarnesyltranstransferaseHumansImidazolesIn Vitro TechniquesLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMembrane GlycoproteinsMicroscopy, Electron, TransmissionMitochondriaNeoplastic Stem CellsProtein Kinase CProtein Kinase C betabcl-2-Associated X Protein