Table 3.

Mechanisms of chemoresistance (MOC) in AML.

Type of Molecular Alteration	Molecule	Reference
Proteins and enzymes	P-gp, MRP1, LRP, GST, TopoII and PKC	[18,36]
Genes	FLT3, WT1, RAS family, MDR1 (ABCB1), SAMHD1, EZH2 and KDM6A have been proposed	[12,36]
miRNAs	Group I, high expression associated with sensitivity: miR-10, miR-27a, let-7a, let-7f, miR-96, miR-128, miR-135a, miR-181a, miR-181b, miR-331 and miR-409. Group II, high expression associated with resistance: miR-20a, miR-32, miR-155, miR-125b, miR-126, miR-210, miR-3151, miR-196b, miR-199a, miR191, miR128, HOTAIR and HOTAIRM1	[33]
Signaling pathways	PI3K/AKT/mTOR, STAT5/PIM, RAS/MAPK, P53, NF-κB, Hh and UPR	[18,36]
Molecules related to drug metabolism	In the case of Ara-C: CDA: irreversibly deaminates Ara-C, changing it to its inactive form, Ara-U SAMHD1: reduces the level of active Ara-CTP through hydrolysis to inactive Ara-C	[37]
Interaction with the tumor microenvironment	SDF-1/CXCR4, FGF2/FGFR1 and VCAM/VLA4 ligand/receptor interaction generates drug resistance similar to FLT3. Hypoxia and acidic pH by maintaining quiescence of leukemic stem cells.	[36]