Table 4:

HSC and LSC phenotypes resulting from genetic alterations in the TGF-βpathway

Gene	Alteration	Phenotype	Reference
TgfprI	cKO (Mx1-Cre)	-no effect on HSC self-renewal, differentiation, or long-term repopulation capacity	Larsson et al 2003
	Pharmacological inhibition	-Inhibitors Ly364947 and SD208 suppress CML LSC colony formation -combination of TGFp inhibition and imatinib decrease CML LSC function	Naka et al 2010
		Inhibitor SB431542 sensitizes CML cell lines to imatinib treatment by reducing Lyn kinase turnover	Smith et al 2012
		Combination of TGFp neutralizing antibody 1D11 and CXCR4 inhibitor in FLT3-mutated AML model decreases leukemic burden and prolongs survival	Tabe et al 2013
Tgfp1	KO	Homozygous mice are embryonic lethal with increased inflammatory response	Kulkarni et al 1993
Tgfp1	cKO in megakaryocytes (Pf4-Cre)	-HSC activation and proliferation	Zhao et al 2014
Tgfpr2	KO	Homozygous mice are embryonic lethal with increased inflammatory response	Oshima et al 1996
Tgfpr2	cKO (Mx1-Cre)	Increased HSC cycling and reduces long-term repopulation capacity	Yamazaki et al 2011
Smad4	cKO (Mx1-Cre)	Impaired HSC self-renewal and reconstitution capacity	Karlsson et al 2007
		Deletion of Smad4 in HOXA9- and NUP98-HOXA9- induced AML model increases LSC frequency	Quere et al 2011
Smad7	Retroviral Overexpression	-increased HSC self-renewal, but no impact on reconstitution or differentiation capacities	Blank et al 2006
p57Kip2	cKO (Mx1-Cre)	-impaired HSC self-renewal and reconstitution capacity	Matsumoto et al 2011