Table 1.

Models used to characterize HIF1A and HIF2A as oncogenes in leukemias.

Leukemia	Cell types	Mouse models	HIFs inhibition or overexpression	Phenotypes	Reference
CML	Human cells
	K562	Nude (in subcutaneous)	Human HIF1A cDNA + l-ascorbic acida	No decreased tumor growth	(83)
	Mouse cells
	Vav-Cre-HIF1aflox/flox transduced with BCR–ABL retrovirus	C57BL/6 J	Vav-Cre-Hif1aflox/flox system	No leukemia induction in second transplantationDecreased LSCs number	(87)
AML	Human cells
	Primary	NOD-SCID	Echinomycinb	Decreased/eliminated leukemia cells	(84)
				No leukemia induction in serial transplantation
	Primary	NOD-SCID gamma	shHIF2A	Decreased/no engraftment	(90)
	HL-60	NOD-SCID gamma	shHIF2A	Increased mice survival	(82)
	NB4	NOD-SCID gamma	shHIF1A, shHIF2A, or EZN-2968c	Increased mice survival	(85)
				Delayed leukemia progression
	SKNO-1	Athymic nude	Echinomycinb	Decreased tumor growth	(79)
	HL-60	Nude (in subcutaneous)	l-ascorbic acida	Decreased tumor growth	(83)
	Mouse cells
	PML-RARα Lin−	129Sv	Ex vivo electroporation with EZN-2968c	Increased mice survival	(85)
	PML-RARα Lin−	129Sv	EZN-2208c	Increased mice survival	(95)
			ATRAd + EZN-2208c	Synergy of both treatments to leukemia eradication
				No leukemia induction in serial transplantation
	FDCP1	DBA/2	Human HIF2A cDNA	Accelerated leukemia progression	(82)
	Relapsed MllPTD/WT:Flt3ITD/WT	C57BL/6 Ly5.1	Echinomycinb	Decreased AML blasts (≤20%)	(92)
				Increased mice survival
	A/E9a transgenic mouse cells	C57BL/6 J	Human HIF1A cDNA	Enhanced leukemia disease	(79)
			siHIF1A	Suppressed leukemia disease
ALL	Human cells
	Jurkat	Transwell matrigel-coated chambers	Hypoxia (2% O2)	Increased tumor invasion	(94)
	Sup-T1
	Primary T-ALL	NOD-SCID gamma	shHIF1A	Increased mice survival	(93)
				Decreased LSCs frequency
	Mouse cells
	Primary (NOTCH1-ΔE/NGFR retrovirus)	NOD-SCID gamma	Hif1aloxP/loxP/CreERT2/GFP system	Increased mice survival	(93)

^al-ascorbic acid indirectly inhibits HIF-1alpha expression by inhibiting NF-κB translocation into the nucleus (83).

^bEchinomycin binds the core-binding site of HIF-1alpha and inhibits its DNA-binding activity (96).

^cEZN-2968 and EZN-2208 specifically target HIF-1alpha (85, 95, 97).

^dATRA target RARα moiety in PML-RARα mutation of APL (95).