Other options for Ph-positive ALL include the use of second-generation TKIs, which have higher BCR-ABL1 affinity and are effective in many patients with resistance to first-generation TKIs, for example, due to de novo variant BCR-ABL1 isoforms or imatinib resistance-conferring mutations at the BCR-ABL1 kinase domain. This evidence concerns the gene ABL1 and acute lymphoblastic leukemia.