Imatinib, dasatinib, and nilotinib are approved both by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for first- or subsequent-line use. Busutinib and ponatinib have recently been approved by the FDA for patients with resistance (or intolerance) to prior TKI therapy. Amino acid substitutions reported to be capable to survive imatinib therapy are almost 50.³  For patients harboring T315I, pharmacologic options include the recently FDA-approved ponatinib (for CML and Ph⁺ ALL patients with resistance to a prior TKI therapy)⁴  or omacetaxine mepesuccinate,⁵  an alkaloid with a mechanism of action other than Bcr-Abl kinase inhibition (for CP or AP CML patients with resistance to 2 or more TKIs).

? indicates that bosutinib-resistant mutations other than T315I and ponatinib-resistant mutations, if any, still need to be assessed.

Y253F/H, E255K/V, F359V/I/C retain insensitivity also to nilotinib.^6,7 

V299L and F317L/V/I/C retain insensitivity also to dasatinib.^7-9 

T315I is a pan-resistant mutation retaining insensitivity to dasatinib, nilotinib, and bosutinib.¹⁰