Role of TIRAP in Myelodysplastic Syndromes
Abstract
This report investigated the potential role of TIRAP activation in BMF in del(5q) MDS. Using a mouse bone marrow transplant model, we have identified some key cellular mechanism in TIRAP-induced BMF. We have shown that TIRAP-induced IFN is a facilitator of BMF. The non-cell autonomous signaling is also responsible for the decrease in myeloid progenitor cell and the increase in progenitor apoptosis. While TIRAP-expressing myeloid cells may initiate an IFN response in the transplant model, non-clonal T cells are responsible for the dramatic increase in IFN expression. Our result also suggests that this TIRAP-induced BMF may not be through the canonical pathway. Interestingly, MDS patients with low risk for leukemic transformation also showed an enriched IFN signature, but not canonical innate immune signaling. We will still need to explore the signaling pathway downstream of TIRAP in our model. Finally, while there is a lack of evidence showing the presence of somatic mutations in the innate immune signaling genes in myeloid neoplasm, there is evidence of dysregulation of the pathway by aberrant epigenetic modification.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2015
- Accession Number
- ADA620605
Entities
People
- Linda Y. Chang
Organizations
- BC Cancer Agency