The most prevalent subtypes of B-ALL frequently have a prenatal origin, following a two-hit model: (1) Somatic acquisition of oncogenic fusion genes (such as ETV6::RUNX1 or TCF3::PBX1) or aberrant chromosome numbers (e.g., high hyperdiploidy) occurs in hematopoietic stem or progenitor cells as a first genetic alteration arising during prenatal life. The gene discussed is ETV6; the disease is acute lymphoblastic leukemia.