ABL1 and cancer: Initial clinical response of CML patients to TKIs is often excellent.(2–5) However, relapse and disease progression characterized by drug resistance occurs even with continuous drug administration, and patients with TKI resistant CML may still succumb to their disease.(6–12) Studies regarding TKI resistance in leukemia have mostly centered on cancer genetic alterations,(13, 14) for example, acquired mutations (which happen in about 1/3 of progressive cases) in the kinase domains of BCR::ABL1 that reduce or even fully impair TKIs’ binding to ABL kinase.