Thus, the detection of pre-existing mutations (PEMs) in primitive stem/progenitor (CD34+) cells may have therapeutic and prognostic implications and is likely to be helpful in optimizing the management of CML patients, specifically after availability of three tyrosine kinase inhibitors as first-line treatment of CML which vary in their effectiveness against different BCR-ABL mutants as well as after FDA approval of ponatinib for TKI-resistant CML, particularly the most aggressive T315I-mutant CML [19]–[23]. The gene discussed is ABL1; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.