Alternative Inhibition Strategy For Treating Acute Promyleocytic Leukemia
- Date:
- April 13, 2007
- Source:
- Journal of Clinical Investigation
- Summary:
- The acid form of vitamin A (retinoic acid; RA) is used to treat a type of leukemia known as acute promyleocytic leukemia (APL). It works by binding to its receptors (retinoic acid receptors, RARs) and driving the leukemic cells to mature and die, rather than remain blocked at a highly proliferative immature stage of development. Researchers from the Fred Hutchinson Cancer Research Center in Seattle have now shown that a protein complex known as CaMKII inhibits RAR activity and that CaMKII inhibitors drive leukemic cells to mature and die.
- Share:
The acid form of vitamin A (retinoic acid; RA) is used to treat a type of leukemia known as acute promyleocytic leukemia (APL). It works by binding to its receptors (retinoic acid receptors, RARs) and driving the leukemic cells to mature and die, rather than remain blocked at a highly proliferative immature stage of development.
Researchers from the Fred Hutchinson Cancer Research Center in Seattle have now shown that a protein complex known as CaMKII inhibits RAR activity and that CaMKII inhibitors drive leukemic cells to mature and die, thereby identifying a potential alternative treatment for individuals with RA-sensitive APL.
In the study, which appears online on April 12 in advance of publication in the May print issue of the Journal of Clinical Investigation, Steven Collins and colleagues show that in human myeloid leukemia cell lines the CaMKII CaMKII-gamma interacts with RAR and inhibits its function by phosphorylating RAR-alpha, thereby enhancing the interaction between RAR-alpha and transcriptional corepressors.
Furthermore, an inhibitor of CaMKs, KN62, induced myeloid leukemia cell lines to mature, leading the authors to suggest that CaMKII-gamma might provide a new target for the treatment of individuals with RA-sensitive myeloid leukemias.
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