In DS-ALL, recent studies of sub-clonal and single-cell evolution of changes in leukemic ALL blasts have identified signaling activators (CRFL2-rearrangements, JAK2 mutations, RAS-MAPK mutations and iAMP21) as frequent events in primary and relapsed leukemic blasts [20, 21, 36]. This evidence concerns the gene JAK2 and acute lymphoblastic leukemia.