Determination of caspase-3 activation fails to predict chemosensitivity in primary acute myeloid leukemia blasts.
BACKGROUND
Ex-vivo chemosensitivity tests that measure cell death induction may predict treatment outcome and, therefore, represent a powerful instrument for clinical decision making in cancer therapy. Such tests are, however, work intensive and, in the case of the DiSC-assay, require at least four days. Induction of apoptosis is the mode of action of anticancer drugs and should, therefore, result in the induction of caspase activation in cells targeted by anticancer therapy.


METHODS
To determine, whether caspase activation can predict the chemosensitivity, we investigated enzyme activation of caspase-3, a key executioner caspase and correlated these data with chemosensitivity profiles of acute myeloid leukemia (AML) blasts.


RESULTS
There was, however, no correlation between the ex-vivo chemosensitivity assessed by measuring the overall rates of cell death by use of the DiSC-assay and caspase-3 activation.


CONCLUSIONS
Thus, despite a significant reduction of duration of the assay from four to one day, induction of apoptosis evaluated by caspase-3 activity does not seem to be a valid surrogate marker for chemosensitivity.
Staib
Peter
P
Clinic I for Internal Medicine, The University Hospital of Cologne, Kerpener Str. 62, 50924 Cologne, Germany. peter.staib@uni-koeln.de
Tiehen
Jan
J
Strunk
Timo
T
Schinköthe
Timo
T
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis* / Q000378:metabolism*; D016923:Cell Death; D045744:Cell Line, Tumor; D003561:Cytarabine / Q000494:pharmacology; D003630:Daunorubicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013050:Spectrometry, Fluorescence; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D000970:Antineoplastic Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D003561:Cytarabine; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C022616:thiazolyl blue; D003630:Daunorubicin