Table 4 Mutations that have been consistently reported in the literature to confer resistance to 2G TKIs, ponatinib and asciminiba.

From: European LeukemiaNet laboratory recommendations for the diagnosis and management of chronic myeloid leukemia

Mutations conferring resistance to dasatinib

V299L, T315I/A, F317L/V/I/C

Mutations conferring resistance to nilotinib

Y253H, E255K/V, T315I, F359V/I/C

Mutations conferring resistance to bosutinib

E255K, V299L, T315I

Mutations conferring resistance to ponatinib

T315M/L

Mutations conferring resistance to asciminibb

G109D, Y115N, M244V, V289I, A337V/T, E355G, F359V, E462K, G463D/S, P465S, V468F, S501R, I502L

  1. aCombinations of mutations in cis on the same BCR::ABL1 molecule (compound mutations) are likely to display peculiar resistance profiles, different to those the individual mutants would display if present in trans on different molecules (i.e., independent clones). However, the in vivo data needed to complement in vitro IC50 predictions are scarce, so precise indications cannot be formulated. It is likely that the great majority of compound mutations will be resistant to imatinib and 2G TKIs. Some T315I-inclusive compound mutations have so far been reported in ponatinib-resistant patients [120, 132] and also in asciminib-resistant patients [140].
  2. bFor asciminib-resistant mutations, the list is provisional and includes mutations within and outside the TKD reported to have been selected in patients who failed asciminib in published clinical trials [136,137,138,139]. These patients had been pretreated with multiple TKIs and further data will be needed to compile a more robust list.
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