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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.
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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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The above post is reprinted from materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


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Journal of Clinical Investigation. "Alternative Inhibition Strategy For Treating Acute Promyleocytic Leukemia." ScienceDaily. ScienceDaily, 13 April 2007. <www.sciencedaily.com/releases/2007/04/070412171344.htm>.
Journal of Clinical Investigation. (2007, April 13). Alternative Inhibition Strategy For Treating Acute Promyleocytic Leukemia. ScienceDaily. Retrieved September 3, 2015 from www.sciencedaily.com/releases/2007/04/070412171344.htm
Journal of Clinical Investigation. "Alternative Inhibition Strategy For Treating Acute Promyleocytic Leukemia." ScienceDaily. www.sciencedaily.com/releases/2007/04/070412171344.htm (accessed September 3, 2015).

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