Despite the success of ponatinib and its recent approval for the treatment of TKI resistant patients, a new study shed light on three newly identified BCR-ABL mutations, L248R, T315V and F317R, detected in CML and Ph+ ALL patients that appear to exhibit differential resistance to TKIs, including the third-generation inhibitors ponatinib and DCC-2036, underscoring the need for novel therapies for resistant Ph+ CML and ALL [17]. Here, ABL1 is linked to acute lymphoblastic leukemia.