When chronic myeloid leukemia harbors the BCR::ABL1 T315I substitution — known as the gatekeeper mutation — standard treatment options are not effective. This molecular finding defines a distinct clinical scenario that requires a specifically tailored therapeutic approach.
The T315I gatekeeper mutation in BCR::ABL1 confers resistance to all currently available tyrosine kinase inhibitors except a small number of agents specifically active against it. Detection of this mutation — at diagnosis or during disease course — is critical for appropriate treatment selection.
Management involves kinase inhibitors with demonstrated activity against the T315I mutation, with treatment response monitored through BCR::ABL1 transcript levels and dose adjustments guided by molecular milestones.
DOI: 10.1002/ajh.27443