Clinical and Molecular Characterization of Familial Marrow Failure Syndrome

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DESCRIPTION (provided by applicant): The inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of disorders characterized by marrow failure, congenital anomalies, and predisposition to myelodysplastic syndromes (MDS). Studies of IBMFS to date have largely focused on pediatric patients, but these are increasingly recognized in adults presenting with cytopenia(s). There are no paradigms defining the optimal care of adult patients with IBMFS. A significant subset of patients fail to fall within the known categories of IBMFS. The diagnosis and medical care of IBMFS patients are limited by our lack of knowledge regarding genetic causes. We will pursue complementary bidirectional studies moving between the pediatric/adult clinics and the laboratory to investigate the clinical features, genetic etiology, and pathophysiology of IBMFS. We will also exploit recent technological advances as a platform to develop novel diagnostic tests for these syndromes. The identification of molecular pathways contributing to marrow failure should provide insights into global molecular pathways regulating hematopoiesis as well as inform our understanding of acquired marrow failure and MDS in the general population. PUBLIC HEALTH RELEVANCE: Understanding the genetic pathways contributing to marrow failure will allow the development of new diagnostic tests and rationally designed medical therapies. Elucidating the molecular mechanisms underlying inherited marrow failure will provide insights into marrow failure arising in the general population.