The SOKAL score in chronic myeloid leukaemia (CML) was traditionally used to stratify patients. With TKI therapy, which mutation in the BCR-ABL kinase domain confers resistance to imatinib, dasatinib, and nilotinib but is sensitive to ponatinib?

• A E255K mutation
• B T315I (gatekeeper mutation) ✓
• C M244V mutation
• D Y253H mutation

Explanation

The T315I (threonine-to-isoleucine) gatekeeper mutation substitutes a hydroxyl group required for hydrogen bonding with imatinib, dasatinib, nilotinib, and bosutinib. It renders the kinase domain inaccessible to all first- and second-generation TKIs. Ponatinib (a third-generation TKI) uses a carbon-carbon triple bond to bypass the T315I steric obstruction and is the treatment of choice. Asciminib (STAMP inhibitor) is another option. Detection of T315I in CML requires switch to ponatinib or asciminib.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.