Assessment of the downstream portion of the mitochondrial pathway of caspase activation in patients with acute myeloid leukemia
- 3 October 2005
- journal article
- Published by Springer Science and Business Media LLC in Apoptosis
- Vol. 10 (6), 1285-1294
- https://doi.org/10.1007/s10495-005-2764-4
Abstract
Most chemotherapeutic agents used in the treatment of acute myeloid leukemia (AML) induce apoptosis by triggering the mitochondrial pathway of caspase activation. To investigate the downstream portion of the mitochondrial pathway of caspase activation in patients with AML, cytosolic lysates were stimulated with cytochrome c and dATP and hydrolysis of Ac-DEVD-AFC by effector caspases was measured. Defects in the distal mitochondrial pathway were more common in samples from patients with AML that relapsed rapidly after induction chemotherapy compared to samples from treatment naïve patients. The incidence of blocked pathways did not differ based on response to induction chemotherapy, as even nonresponders generally had an intact pathway. When the distal mitochondrial pathway was blocked, defects were usually at the level of the effector caspases. Thus, functional defects in the distal portion of the mitochondrial pathway of caspase activation may help explain the nature of response and relapse after treatment.Keywords
This publication has 32 references indexed in Scilit:
- A Unified Model for Apical Caspase ActivationMolecular Cell, 2003
- Chemotherapy: targeting the mitochondrial cell death pathwayOncogene, 2002
- A matter of life and deathCancer Cell, 2002
- Mitochondria as targets for established and novel anti-cancer agentsDrug Resistance Updates, 2001
- Respiratory Chain-Generated Oxidative Stress Following Treatment of Leukemic Blasts with DNA-Damaging AgentsExperimental Cell Research, 2001
- Role of cytochrome c and dATP/ATP hydrolysis in Apaf-1-mediated caspase-9 activation and apoptosisThe EMBO Journal, 1999
- Proteases to die forGenes & Development, 1998
- The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of ApoptosisScience, 1997
- Probability of long-term disease-free survival for acute myeloid leukemia patients after first relapse: A single-centre experienceAnnals of Oncology, 1996
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976