Bcr-Abl T315I mutant protein (Bcr-Abl T315I)

The Bcr-Abl T315I mutant protein is a variant of the Bcr-Abl fusion tyrosine kinase, arising from a point mutation at amino acid position 315 where threonine is replaced by isoleucine. This mutation confers resistance to most tyrosine kinase inhibitors (TKIs) used to treat chronic myeloid leukemia (CML), except for ponatinib. The T315I mutation maintains or increases Bcr-Abl tyrosine kinase activity, promoting cell proliferation and survival. It disrupts hydrogen bonding with TKIs due to steric hindrance caused by the isoleucine substitution. Therapies targeting this mutation are crucial for overcoming drug resistance in CML.

Other names

BCR-ABL1 T315IT315I Bcr-AblBCR-ABL1 with T315I mutationBcr-Abl1 T315I kinase domain mutant

ATP-competitive tyrosine kinase inhibitor; Ponatinib overcomes steric hindrance caused by T315I mutation.