The biology of B-ALL is determined mainly by the first genetic hit, which is usually a change in chromosome numbers (hyperdiploidy or hypodiploidy) or a chromosomal translocation (e.g. t(4;11) MLL-AF4 or t(12;21) ETV6-RUNX1) (Table 1). The gene discussed is RUNX1; the disease is acute lymphoblastic leukemia.