Using a mouse model with myelodysplastic syndromes (MDS), researchers at the Cincinnati Children’s Hospital Medical Center found that the overexpression of TRAF6 in hematopoietic cells is a potential driver of MDS. If confirmed in human models, these findings, published in Nature Immunology, could lead to the identification of potential treatment targets for cases of MDS triggered by an overexpression of TRAF6, according to the study authors.
“We found that TRAF6 overexpression in mouse hematopoietic stem cells results in impaired blood cell formation and bone marrow failure,” said Daniel Starczynowski, PhD, from the Division of Experimental Hematology and Cancer Biology at Cincinnati Children’s Hospital, and lead author of the study. “A number of therapeutic approaches can be tested and directed against TRAF6 and other related proteins responsible for MDS.”
The authors tested mouse models and human samples of MDS/acute myeloid leukemia and found a novel substrate of TRAF6 called hnRNPA1 – an RNA binding protein. They also observed molecular interactions with Cdc42, a protein that helps regulate cells implicated in cancer. Both of these proteins could serve as potential treatment targets, but future studies will need to test their therapeutic potential.
Source: Fang J, Bolanos LC, Choi K, et al. Ubiquitination of hnRNPA1 by TRAF6 links chronic innate immune signaling with myelodysplasia. Nat Immunol. 2016 December 26. [Epub ahead of print]