Abstract
Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome characterized by hypoproliferative anemia, in which the major defect is ineffective erythropoiesis. Over 70% of patients with DBA have mutations in ribosomal protein subunits, although the precise molecular mechanisms contributing to the pathogenesis of DBA are not well understood. The current standard of care for patients with DBA includes steroids, chronic red cell transfusions, or stem cell transplantation, but these are all associated with significant morbidities including infections, iron overload, and the risk of graft versus host disease. Therefore, the development of more effective and less-toxic therapies is needed to treat the anemia seen in patients with DBA. Recently, we identified Nemo-like Kinase (NLK) as a potentially novel therapeutic target for a more feasible treatment option for patients with DBA. Given that various types of mutations in ribosomal subunits are associated with DBA, pharmacologically targeting NLK with a small molecule inhibitor as a common target could be a potential therapeutic alternative for the treatment of DBA.
Keywords
Diamond Blackfan Anemia, Inherited bone marrow failure syndromes, Ribosomopathies, Nemo-like Kinase, Erythropoiesis