Table 1. Summary of the main inhibitors for acute myeloid leukemia targeted therapy.

Agents	Target and mechanisms of actions
Hypomethilating agents	Hypermethylation at CpG islands within promoter region can lead to silencing of tumor-suppressor genes and gene inactivation, acting as an alternative mechanism to deletions and mutations; the methylation of tumor-suppressor genes and silencing of DNA are chromatin remodeling factors that can contribute to carcinogenesis.
MDR modulators	Over-expression of multidrug resistance 1(MDR1) gene, encoding P-glycoprotein, reduces the intracellular drugs accumulation, causing resistance to chemotherapy treatment.
Biological agents	Anti-CD33 monoclonal antibodies (trigger downstream signaling cascade and lead to antiproliferative effect); histone deacetylases inhibitors (HDAC removing the acetyl group causes a tighter binding of histones to DNA, preventing gene transcription).
Agents that modulate intracellular signaling pathways	RTKs, docking and adapter proteins and transcription factors are the classes of proteins involved in the signaling, and an inappropriate function of the members of each group was associated with hematological malignancies. Several aberrations have been described in RTKs genes: c-abl, c-fms, flt3, c-kit, PDGFRα/β, and consequently inappropriate activation of downstream signaling cascades, such as Jak-Stat, Ras/MAPK e PI3K/AKT. Each of these proteins may be a therapeutic target, as well as factors directly involved in the regulation of apoptosis (BCL-2, NFkB, caspases, cyclins, inhibitors of cyclins, transcription factors).

MDR, multidrug resistance; RTK, receptor tyrosine kinase; PI3K, phospatidylinositol-3-kinase; AKT, protein kinase B (PKB).