TABLE 3.

Acquired alterations associated with TKI resistance in CML patients

Gene/Pathway	Type of Alteration	Drug	References
BCR-ABL1	Kinase domain point mutations (T315I†, Y253H, E255K, E255V, Y253F, Y253H, F317L, H396P, M351T, and others)	Imatinib, Nilotinib, Dasatinib	[85–89] [90–93]
KIT	Activation/elevated expression	Imatinib	[101, 102]
HIF1A	Activation/elevated expression	Imatinib	[103, 104]
PI3K/AKT	Pathway activation	Imatinib, Nilotinib, Dasatinib	[110, 111]
P38/MAPK	Pathway activation	Imatinib	[112, 113]
JAK/STAT	Pathway activation	Imatinib	[114–117]

^†Note: Ponatinib is equally effective against all kinase domain mutations of BCR-ABL1, including T315I.