Goal 3: Advance Translational Research

Can SYK or BTK inhibition ameliorate autoimmune hemolytic anemia after stem cell transplantation

Experimental mouse models of ITP and AIHA are dependent on FcgR-signaling, which in turn depends on Syk kinase activity for activation of phagocytes. A significant and refractory complication of stem cell transplantation is immune hemolytic anemia. This can be either autoimmune or alloimmune. In either case it is likely that clearance of RBC and RBC progenitors is dependent on extravascular mechanisms involving activation of macrophages and other RE cells via FcgR signaling. Available inhibitors of SYK and BTK are appealing targets for inhibition in this context. There are both FDA-approved inhibitors (eg. ibrutinib, fostamatinib) as well as drugs in development (entospletinib) that can be best assessed in a Network context

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Idea No. 449