In Ph-positive ALL, therapy has shifted from intensive chemotherapy and allogeneic SCT before 2000 to regimens combining BCR::ABL1 TKIs with intensive or lower intensity chemotherapies followed by allogeneic SCT (2000–2010), the addition of ponatinib to intensive chemotherapy (2010–2018) demonstrating for the first time that allogeneic SCT may not be a requirement for a better cure, and finally the recent shift to (mostly) non-chemotherapy non-SCT targeted strategies with BCR::ABL1 TKIs and blinatumomab. This evidence concerns the gene ABL1 and acute lymphoblastic leukemia.