Illustration of clonal evolution from in utero leukemia initiation (prenatal) to remission (postnatal). Strikingly, UBA2 deletion proceeded ETV6-RUNX1 fusion generated by the shared complex rearrangement in utero. Fifty-seven additional shared SNVs/indels were acquired during the prenatal period. Clonal evolution of preleukemic clones established prenatally in both twins continued separately, mainly postnatally, acquiring SVs and SNVs/indels unique to each twins’ leukemia. Genes known to be recurrent targets of secondary events in BCP-ALL, ATF7IP, RAG1/RAG2, and ETV6, were targeted by unique analogous deletions in both twins. The UBA2 deletion persisted subclonally in remission of both twins. dPCR results stated in percent refers to the fraction of mutant target DNA in the analyzed sample.