The Role of mDia1 in the Aberrant Innate Immune Signaling in del(5q) Myelodysplastic Syndromes
Technical Report,15 Sep 2016,14 Sep 2017
Northwestern University Evanston United States
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Myelodysplastic syndromes MDS are a group of diseases affecting bone marrow and blood with an increased risk of developing acute leukemia. Many genomic abnormalities are associated with MDS with deletion of chromosome 5q being the most common. Our recently published work demonstrated that loss of mDia1, a protein with its encoding genes located at chromosome 5, led to the activation of the innate immune response through an aberrant overexpression of CD14 on granulocytes, which accelerate the development of MDS in mDia1deficient mice. Based on this study, we hypothesis that CD14 induced abnormal immune response is critical in the pathogenesis of MDS. In the past grant reporting cycle, we have successfully demonstrated the significance of in vivo damage associated molecular patternsDAMPs in the pathogenesis of MDS. Significant achievements were also obtained in other major goals. We demonstrated the efficacies of CD14, AP1, and SP1 inhibitors in the down regulation of CD14 in granulocytes in vitro and in vivo. CD14 and mDia1 double knockout are also generated and we expect to have data in a few months. There are no major changes of the experimental designs.
- Medicine and Medical Research