Somatic mutations and chromosomal rearrangements involving RUNX1 loss-of-function or changes of its transcriptional activity are frequently observed in myelodysplastic syndrome and leukemias of myeloid and lymphoid lineages, such as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myelomonocytic leukemia (CMML). This evidence concerns the gene RUNX1 and acute lymphoblastic leukemia.