Table 1. Oncogenic mutations typically impair HSC maintenance.

The effects of oncogenic mutations on HSC analyzed in genetically engineered mice. Data summarized for effects on HSC were, at least in large part, derived from analyses of unperturbed young mice (HSC at steady-state).

Genotype	Pathway Deregulated	Effect on HSC	Corollary	References
Rb cKO	CDK/Rb/E2F	↓self-renewal	↑cell cycle	(74–76)
p21CIP1−/−	CDK/Rb/E2F	↓self-renewal	↑cell cycle	(77)
PTEN cKO	PI3K/AKT/mTOR	↓self-renewal	↑differentiation; ↑cell cycle	(58, 59)
p16INK4A−/−	CDK/Rb/E2F	↓self-renewal	↑cell cycle	(71)
ATM−/−	DDR/metabolism	↓self-renewal	↑ROS	(78)
p53−/− & cKO	p53	no effect		(72, 73)
GSK3 knockdown & GSK3b−/−	Wnt/β-catenin mTOR	↓self-renewal; loss of HSC	↑cell cycle	(79)
APC cKO	Wnt/β-catenin mTOR	↓self-renewal	↑differentiation; ↑ROS	(80)
TSC1−/−	mTOR	↓self-renewal	↑differentiation; ↑ROS	(81, 82)
LKB cKO	mTOR/AMPK	↓self-renewal	↑apoptosis ↑cell cycle	(83)
EGR1−/−	various	↓self-renewal; HSC exhaustion	↑cell cycle; ↑mobilization	(84)
FBW7 cKO	Notch; Myc; Cyclin E	↓self-renewal; ↓CRC	↑cell cycle; ↑Myc; ↑apoptosis	(85, 86)
MEN1 cKO	Interacts with	↓hematopoietic	↓↓HSC function	(87)
(MENIN)	MLL	output; ↓CRC	under stress
c-CBL−/−	Tyrosine kinase signaling	↑HSC#; ↑CRC	↑cell cycle; ↑STAT5 activation	(62)
Ikaros LOF mt	Ikaros	↓self-renewal; loss of HSC	impaired differentiation	(88–90)
β-catenin activation	Wnt/β-catenin/mTOR	loss of HSC; ↓differentiation	↑apoptosis ↑cell cycle	(91–93)
Myc o/e	Myc	↓self-renewal	↑cell cycle	(94)
Rheb2 o/e	mTOR	↓self-renewal	↑cell cycle	(95)
Kras(G12D)	Ras/MAPK	↑CRC; ↓↓HSC #	↑cell cycle	(66)
Bcr-Abl (inducible)	Ras, AKT, STAT, others	↓HSC #; ↑CRC	↑cell cycle; ↑differentiation	(67)

cKO, conditional knockout; o/e, transgenic overexpression; CDK, cyclin-dependent kinase; CRC, competitive repopulating capacity.