The effects of combination treatments on drug resistance in chronic myeloid leukaemia: an evaluation of the tyrosine kinase inhibitors axitinib and asciminib

Table 1 \(\widetilde {\text {IC}}_{50}\) (IC₅₀ of mutant relative to wildtype, Eq. 4) values of Bcr-Abl1 mutants

Mutant ^a	Imatinib	Nilotinib	Dasatinib	Bosutinib	Ponatinib	Axitinib ^b	Asciminib
P223S	0.70	0.82	0.83	0.72	0.86		24.62
G250H	0.85	1.06	0.98	0.72	0.94		1.21
Q252H	2.78	2.41	1.44	0.98	5.56	1.92	17.96
Y253H	15.95	34.89	1.84	0.91	5.28	1.31	2.81
E255K	12.51	13.99	7.53	4.07	11.82		3.86
E255V	10.98	27.60	3.76	2.65	11.28	1.25	1.92
K294E	0.48	0.68	0.48	0.55	0.67		29.99
V299L	1.83	1.81	10.33	13.65	1.22	0.32	10.07
T315I	27.70	266.76	806.32	17.07	5.59	0.16	12.56
A337V	0.91	1.04	0.98	0.98	0.95		744.64
E355G	2.56	1.37	0.71	0.63	0.77		15.34
F359V	4.00	7.58	1.45	1.04	4.70	0.69	18.98
E459K	2.22	2.62	0.82	0.68	2.01		4.94
P465S	1.02	0.94	0.82	0.79	0.98		605.96
V468F	0.72	0.68	0.48	0.74	0.42		529.32
I502L	0.62	0.76	0.70	0.67	0.78		49.72

\(\widetilde {\text {IC}}_{50}> 1\) indicates a mutation that is resistant to some degree. Note that drugs can sometimes effectively suppress weakly resistant mutations. Given values are the geometric mean of the \(\widetilde {\text {IC}}_{50}\) from all sources that state a precise value (i.e. not an approximation, lower, or upper bound) for the given mutation [9–11, 15, 33–44]. The specific sources associated with each value are given in Additional file 2
^aMutant selection was based on limited data availability for asciminib. Mutations at underlined residues are only associated with asciminib resistance (preclinical data)
^bData for axitinib is only known for a limited subset of mutations but it is considered to be ineffective to native Abl1 and all resistance mutants except T315I and possibly V299L and F359V

ISSN: 1471-2407