Table 2.

The preclinical application of autophagy modulation in targeted therapies for different subtypes of AML

AML subtype	Autophagy Regulation	Autophagy Modulator	Molecular Targeted Therapy Combined with	leukemic model		Benefits from Autophagy Regulation	Refs
				cell line in vitro	cell lines/ xenografted animals
FLT3-mutated	autophagy suppression	PIK3C3/VPS34 inhibitor SAR405	–	MOLM-14 with FLT3-ITD and FLT3-D835Y	–	overcomes acquired resistance to FLT3 inhibitors	[40]
	autophagy suppression	shRNA against ATG12	–	–	MOLM-14 with FLT3-D835Y	overcomes acquired resistance to FLT3 inhibitors	[40]
	autophagy suppression	lysosomal autophagy inhibitor Lys05	FLT3 TKI inhibitor Quizartinib	MV4-11, MOLM-13 with FLT3-ITD	–	enhances sensitivity of FLT3-ITD+ AML cells to TKI treatment	[41]
	autophagy improvement	Proteasome inhibitor bortezomib	FLT3 TKI inhibitor Quizartinib	MOLM-14 with FLT3-ITD and FLT3-D835Y	MOLM-14 with FLT3-ITD and FLT3-D835Y	overcomes acquired resistance to FLT3 inhibitors	[45]
	autophagy improvement	RET inhibitor vandetanib	FLT3 TKI inhibitor crenolanib	MV4-11, MOLM-13 with FLT3-ITD; MONO-MAC-6 with FLT3-V592A	–	enhances sensitivity of FLT3-ITD+ AML cells to TKI treatment	[46]
NPM1-mutated	autophagy suppression	shRNA against PML	–	OCI-AML3 with NPM1 mutation type A (NPM1-mA)	–	serves as a potential strategy for NPM1-mutated AML therapy	[51]