Cincinnati Children's Hospital researchers report in Nature Immunology a new mechanism that controls blood cell function and several possible molecular targets for treating myelodysplasia syndromes (MDS) - a group of pre-malignant disorders in which bone marrow does not produce enough healthy blood cells. MDS can lead to acute myeloid leukemia (AML), a fast-spreading blood cancer that can be deadly if not treated promptly. A research team led by cancer biologist Daniel Starczynowski, Ph.D., found that over-expression of a protein called TRAF6 (image) in hematopoietic cells drives the onset of MDS. TRAF6 normally functions as an immune sensor of pathogens, according to the authors, who published their data online on December 26, 2016. The Nature Immunology article is titled “Ubiquitination of hnRNPA1 by TRAF6 Links Chronic Innate Immune Signaling With Myelodysplasia.” "We found that TRAF6 over-expression in mouse hematopoietic stem cells results in impaired blood cell formation and bone marrow failure," said Dr. Starczynowski, a member of the Division of Experimental Hematology and Cancer Biology at Cincinnati Children's Hospital Medical Center. "Based on our paper, a number of therapeutic approaches can be tested and directed against TRAF6 and other related proteins responsible for MDS." In testing on laboratory mouse models and human MDS/AML samples, the researchers identified a novel substrate of TRAF6 called hnRNPA1, an RNA-binding protein. They also found molecular interactions with Cdc42, a protein that helps regulate cells also implicated in cancer. All of these molecules could be potential treatment targets for cases of MDS triggered by over-expression of TRAF6, according to Dr.
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