Familial Leukemia Associated with Thrombocytopenia

Abstract

Familial predisposition to leukemia has been known for decades. In some families, this condition is also associated with thrombocytopenia and history of bleeding. Germline mutations in the RUNX1 gene have been proven to cause familial platelet disorder with predisposition to myeloid malignancies (FDPMM). The disease typically presents with mild-to-moderate thrombocytopenia with normal-size platelets, functional platelet defects leading to prolonged bleeding, and an increased risk to develop myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or T-cell acute lymphoblastic leukemia (T-ALL). In recent years, molecular defects in other genes, such as ANKRD26 and ETV6, have been associated with thrombocytopenia and susceptibility to hematological malignancy as well. In our chapter, we will present a review of up-to-date knowledge on this topic along with several case studies demonstrating the diagnostic process and management of the affected families.