A CML Patient Carrying BCR::ABL1 Splicing Variants Did Not Experience Blast Crisis for 15 Years without Responding to...

A 45-year-old man was diagnosed with CML in the chronic phase and therefore was sequentially treated with imatinib, dasatinib, nilotinib, and ponatinib. Neither ABL1 point mutations nor any additional chromosomal abnormalities were detected. The patient's best response was a partial cytogenetic response to nilotinib treatment. The deletion of amino acid residues 184-274 and a 35 bp insertion after nucleotide 1423 of ABL1 were detected before ponatinib administration. Two years after ponatinib administration, the patient died of a traumatic brain hemorrhage 15 years after the CML diagnosis. He did not progress to blast crisis, possibly because of the emergence of a loss-of-function ABL1 splicing variant.