In chronic myeloid leukaemia (CML), a patient achieves complete cytogenetic response (CCyR) on imatinib but loses major molecular response (MMR). BCR-ABL kinase domain mutation testing reveals T315I mutation. Which is the ONLY TKI active against this mutation?
- A Ponatinib ✓
- B Dasatinib
- C Nilotinib
- D Bosutinib
Correct answer: A. Ponatinib
Explanation
The T315I ('gatekeeper') mutation in BCR-ABL confers resistance to all first- and second-generation TKIs (imatinib, dasatinib, nilotinib, bosutinib) because it eliminates a critical hydrogen bond. Ponatinib (a third-generation TKI) and asciminib (a STAMP inhibitor) are active against T315I. Ponatinib is the standard choice; asciminib specifically binds the myristoyl pocket and is also effective. This is a high-yield point in resistance management of CML.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.