Assessment of caspase activity as a possible prognostic factor in acute myeloid leukaemia.
Caspases are one of the key effector molecules in apoptosis. Caspase-3 activity (identified by cleavage of the peptide DEVD) was analysed in bone marrow blasts (minimum 70%) from 45 acute myeloid leukaemia (AML) patients. 12 patients (25%) exhibited high levels of specific DEVDase activity. These blast cells, despite having activated caspase-3, displayed none of the classical caspase-dependent morphological characteristics of apoptosis, such as degradation of DNA fragmentation factor 45, DNA fragmentation, and appeared to be more resistant to drug-induced apoptosis. Our results suggest that in these AML cells, resistance to apoptosis occurred downstream of caspase-3 activation.
Oliver
Lisa
L
INSERM U419, IFR 26, Centre Hospitalier Universitaire de Nantes, 9 Quai Moncousu, 44035 Nantes, France. loliver@nantes.inserm.fr
Vavasseur
Fabienne
F
Mahé
Beatrice
B
Perrin
Pascale
P
Harousseau
Jean-Luc
JL
Meflah
Khaled
K
Vallette
François-Marie
FM
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D006801:Humans; D007951:Leukemia, Myeloid / Q000201:enzymology* / Q000473:pathology; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism*; D011379:Prognosis
D010447:Peptide Hydrolases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C108711:DEVDase