Germline RUNX1 mutations are dominant-negative mutations and correlate to a higher risk of developing hematological malignancies compared to RUNX1 loss-of-function mutations [5-8]. It is important to note, however, that such germline mutations alone are not sufficient for the development of leukemia and additional mutations in RUNX1 (bi-allelic mutations) or epigenetic modifiers, splicing factors, or tumor suppressors are required to induce myeloid malignancies [1,4]. This evidence concerns the gene RUNX1 and leukemia.