Table 2:

HSC and LSC phenotypes resulting from genetic alterations in the Wnt/β-catenin pathway

Gene	Alteration	Phenotype	Reference
β-catenin	cKO (Mx1-Cre)	-no effects on HSC function	Cobas et al 2004
		-delays initiation of disease in mouse model of CML, compromised LSC self-renewal	Zhao et al 2007; Hu et al 2009
		-impaired LSC function in MLL-AF9 AML	Wang et al 2010
		-pre-LSCs have impaired ability to generate LSCs in MLL-ENL AML model	Yeung et al 2010
	Conditional expression of activated mutant (Mx1-Cre)	-impaired HSC repopulation, loss of myeloid lineage commitment	Kirtstetter et al 2006; Scheller et al 2006
	Conditional expression of activated mutant (Scl-Cre-ER)	-HSC apoptosis, which can be rescued by activation of the PI3K pathway	Perry et al 2011
Apc	cKO (hypomorphic allele)	Mildly increased Wnt signaling enhances HSC reconstitution in vivo, but higher levels of Wnt signaling impairs engraftment and HSC reconstitution.	Luis et al 2011
Lef/Tcf	Lef cKO (Vav1-iCre) Tcf germline KO	-impaired LSC self-renewal in CML model -normal HSC self-renewal	Yu et al 2016
Wnt5a	Overexpression	-inhibits HSC expansion by inducing a quiescent state at the expense of canonical Wnt signaling	Nemeth et al 2007
	Heterozygous deletion	Loss of one Wnt5a allele leads to spontaneous CML or B cell lymphoma development	Liang et al 2003
	Haploinsufficiency in the bone marrow niche	-impaired HSC engraftment -impaired leukemia engraftment in CML model	Schreck et al 2017