Table 2.

Exemplary LSC Resistance Mechanisms to Clinically Approved AML Therapies.

Drug Class	Name	Potential AML LSC Resistance Mechanisms	References
Anthracyclines	Doxorubicin	NCAM1-mediated constitutive activation of the pro-survival MAPK signaling pathway	[139]
	Daunorubicin	Potentially via upregulated multi-drug resistance transporters	[140,141]
	Idarubicin	CALCRL-mediated DNA damage repair and cell-cycle progression	[138]
Hypomethylating Agent	Azacitidine	Potential deposition of LSCs in the protective BM microenvironment; enhanced OXPHOS machineries	[142,143]
IDH Inhibitor	Ivosidenib/enasidenib	Expression of stemness-associated gene signatures	[57]
FLT3 Inhibitor	Sorafenib	Enhanced stromal interaction and diminished activation of pro-survival signaling mediated by the SDF-1α-CXCR4 axis	[144,145]