Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acute Disease
-
Antigens, CD34
-
Antineoplastic Agents / pharmacology*
-
Apoptosis / drug effects*
-
Cell Survival / drug effects
-
Cells, Cultured
-
Enzyme Activation
-
Humans
-
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
-
JNK Mitogen-Activated Protein Kinases / metabolism
-
Leukemia, Myeloid / physiopathology*
-
Myelodysplastic Syndromes / physiopathology*
-
Stem Cells / drug effects
-
Stem Cells / physiology
-
Sulindac / analogs & derivatives*
-
Sulindac / pharmacology
Substances
-
Antigens, CD34
-
Antineoplastic Agents
-
Sulindac
-
JNK Mitogen-Activated Protein Kinases
-
sulindac sulfone