Table 1.

ALL redox signaling pathway targets and representative drugs.

Signaling Pathway	Targets	Representative Drugs	Antileukemic Effect	Refs
BCR/ABL	Tyrosine kinase inhibitor (TKI)	Imatinib	First-generation TKI that can block the ATP-binding sites of BCR-ABL and prevent activation of the conformation of oncogenic proteins	[85]
		Nilotinib	Second-generation TKI and high-affinity aminopyrimidine-based ATP-competitive inhibitor with more specific inhibition of BCR/ABL activity	[86]
		Dasatinib	Second-generation TKI that can bind to inactive and active BCR/ABL kinase and inhibit Src family kinases and c-Kit	[86]
		Bosutinib	Third-generation TKI and potent dual inhibitor of Src and ABL kinases with longer-term safety than second-generation and other third-generation TKIs	[87]
		Ponatinib	Third-generation TKI that is effective for known mutations in imatinib-resistant genes (including T315I)	[88]
Notch	γ-secretase inhibitor (GSIs)	BMS-906024	Inhibits the activity of Notch signaling by downregulating the expression of multiple known target genes of Notch but has no marked effect on c-Myc	[89]
		PF-03084014	Downregulates the level of the Notch intracellular domain and the expression of Notch target genes Hes-1 and c-Myc and induces cell cycle arrest and apoptosis of T-ALL cells	[90]
PI3K/AKT/mTOR	PI3K-δ inhibitor	Idelalisib	Downregulates the level of AKT phosphorylation in B-ALL cells, inhibits cell proliferation, and blocks the homing of B-ALL cells into the bone marrow	[91]
		NVP-BKM120	Downregulates the phosphorylation levels of AKT and mTOR in T-ALL cells, inhibits cell cycle progression, and promotes apoptosis	[92]
	AKT inhibitor	MK-2206	Downregulates AKT phosphorylation levels in both T-ALL and B-ALL cell lines (it can also promote PTEN phosphorylation in B-ALL cell lines), inhibits cell proliferation, and promotes apoptosis	[93]
	PI3K/mTOR inhibitor	PI-103	More potent than inhibitors that are selective only for PI3K or for mTOR and can effectively induce cell cycle arrest and apoptosis in T-ALL cells	[94]
JAK/STAT	JAK inhibitor	Ruxolitinib	JAK1/2 inhibitor that can reduce ROS and ROS-induced gene expression signatures and inhibit the growth of leukemia cells	[66]
RAS	MEK inhibitor	Selumetinib Trametinib MEK162	Reduce ERK phosphorylation and induce apoptosis in the RAS-mutant MLL-rearranged ALL cells	[95]