What is RUNX1 FPD/AML?

RUNX1 FPD/AML is familial platelet disorder with a predisposition to acute myeloid leukemia. RUNX1 FPD/AML is a pre-leukemic disorder involving a likely autosomal dominant, inherited qualitative/quantitative defect of platelets associated with an approximately 50% lifetime risk of developing AML (an acute form of leukemia). 

The underlying defect is caused by monoallelic mutations in RUNX1 that result in haploinsufficiency. In other words, in RUNX1 FPD/AML, one of the two copies of the RUNX1 gene is dysfunctional. RUNX1 is a transcription factor important for the formation of blood in the embryo from hemogenic endothelium. It is also important for the differentiation of many blood cell lineages including T lymphocytes and megakaryocytes. RUNX1 mutations in hematopoietic stem cells create a “pre-leukemic” stem cell that can ultimately acquire secondary mutations that convert it into a leukemia cell.