Exisulind induces apoptosis in advanced myelodysplastic syndrome (MDS) and acute myeloid leukaemia/MDS.
The influence of Exisulind on the viability and apoptosis of CD34(+) stem cells from patients with advanced myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML)/MDS was investigated. In eight out of 10 patient samples Exisulind reduced the fraction of viable cells by inducing apoptosis. We found evidence that Exisulind-mediated apoptosis depends on c-Jun NH(2)-terminal kinase (JNK) activation. Addition of a specific JNK-inhibitor to Exisulind-treated advanced MDS and AML/MDS cells partly abrogated apoptosis. We propose that Exisulind is tested in clinical phase I/II trials for the treatment of advanced MDS and AML/MDS.
Czibere
Akos
A
Department of Haematology, Oncology and Clinical Immunology, Heinrich Heine-University, Düsseldorf, Germany. aczibere@bidmc.harvard.edu
Prall
Wolf C
WC
Zerbini
Luiz F
LF
Jäger
Markus
M
Kobbe
Guido
G
Knipp
Sabine
S
Libermann
Towia A
TA
Haas
Rainer
R
Aivado
Manuel
M
D000208:Acute Disease; D018952:Antigens, CD34; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000503:physiopathology*; D009190:Myelodysplastic Syndromes / Q000503:physiopathology*; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D013467:Sulindac / Q000031:analogs & derivatives* / Q000494:pharmacology
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D013467:Sulindac; D048031:JNK Mitogen-Activated Protein Kinases; C025463:sulindac sulfone