Abstract
Germline RUNX1 mutations lead to a rare form of autosomal-dominant familial thrombocytopenia with a predisposition for myeloid malignancies and are classified as distinct entities by the WHO. We report a case of B lymphoblastic leukemia developing in a patient with a familial RUNX1 mutation, which is a first in the literature. An FLT3-ITD mutation as well as a balanced chromosomal translocation t(1;7) was present at the time of diagnosis of leukemia, favoring the theory that additional hits or mutations are necessary for malignant transformation in patients with a germline RUNX1 mutation. The transformed disease runs an aggressive course compared to the same malignancy associated with a somatic RUNX1 mutation. Additionally, family members should be screened for the mutation, followed up clinically if they carry the mutation, and should not be used as stem cell donors to treat the affected relatives.