Alternative Inhibition Strategy For Treating Acute Promyleocytic Leukemia

Main Category: Lymphoma / Leukemia / Myeloma
Article Date: 18 Apr 2007 - 3:00 PDT

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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 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.

TITLE: CaMK II regulates retinoic acid receptor transcriptional activity and the differentiation of myeloid leukemia cells

AUTHOR CONTACT:
Steven J. Collins
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

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JCI table of contents: April 12, 2007

Contact: Karen Honey
Journal of Clinical Investigation

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