Table 1.
Summary of human and murine studies describing the function of specific niche components in both normal and malignant hematopoiesis
Niche componentFunction/roleMouse studiesHuman studies
Vascular endothelium AML increases blood vessel formation, marrow angiogenesis, nitric oxide production, vascular permeability, and hypoxia Hussong et al., 2000; Benito et al., 2011; Passaro et al., 2017   
HIF induction associated with B-ALL and AML chemo-resistance Muz et al., 2014; Wellmann et al., 2004   
The CXCR4/CXCL12 axis and adhesive interactions through CD44 promote leukemic cell survival Schneider et al., 2002; Spoo et al., 2007; Passaro et al., 2015; Pitt et al., 2015; Sison and Brown, 2011; Fedorchenko et al., 2013; Godavarthy et al., 2019; Jin et al., 2006; Krause et al., 2006   
MSCs 
MSCs Support IKZF1-mutant B-ALL relapse and may promote chemoresistance, but not in T-ALL Churchman et al., 2015;, Joshi et al., 2014;, Vitanza et al., 2014;, Duan et al., 2014;, Hawkins et al., 2016;, Gomariz et al., 2018;   
AML cells induce osteogenic differentiation Battula et al., 2017   
Associate with SNS to regulate HSC mobilization and regeneration following chemotherapy Ho et al., 2019; Katayama et al., 2006; Lucas et al., 2013; Maryanovich et al., 2018; Méndez-Ferrer et al., 2010; Scheiermann et al., 2012   
CD271+ MSCs Increase in MDS and AML patients; favor blast expansion through CXCL12  Geyh et al., 2013, 2016  
Sinusoid-associated Lepr+ stromal cells Secretion of SCF, critical for HSC function Ding et al., 2012   
Arteriole-associated NG2+ perivascular cells Secretion of CXCL12, critical for HSC function Asada et al., 2017   
Osteolineage cells 
Osteoblasts AML blocks osteogenesis and decreases osteoblast numbers Baryawno et al., 2019; Duarte et al., 2018; Krevvata et al., 2014; Hanoun et al., 2014  Krevvata et al., 2014; El-Ziny et al., 2005; Fitter et al., 2008; Haddy et al., 2001; Sala and Barr, 2007; Shalet, 1996; Sinigaglia et al., 2008  
Disease improvement following chemotherapy correlated with increased osteoblast activity  Crofton et al., 1998; El-Ziny et al., 2005; Fitter et al., 2008  
MDS, MPN, and CML cells remodel endosteal osteoblasts into a self-reinforcing leukemic niche Medyouf et al., 2014; Schepers et al., 2013  Medyouf et al., 2014  
PTHR activation differentially affects BCR-ABL1+ CML-like MPN and MLL-AF9+ AML Krause et al., 2013   
Restricted by MLL-AF9-AML β2-adrenergic signaling Hanoun et al., 2014   
Osx+ cells Dicer-1 deletion leads to MDS Raaijmakers et al., 2010   
SDS mutation drives MDS and predicts AML Zambetti et al., 2016  Zambetti et al., 2016  
Osteoblast precursors and osteoblasts Activated β-catenin leads to MDS/AML Kode et al., 2014; Bhagat et al., 2017; Stoddart et al., 2017  Kode et al., 2014; Bhagat et al., 2017; 
Nestin+ cells SHP2 activating mutations lead to MPN progression Dong et al., 2016   
Expanded by MLL-AF9+AML–induced sympathetic neuropathy Hanoun et al., 2014   
Adipocytes 
Adipocytes Decreased chemotherapy responsiveness in obese pediatric B-ALL and adult AML patients  Castillo et al., 2016; Castillo et al., 2012; Orgel et al., 2016; Orgel et al., 2014  
Sequester and metabolize commonly used chemotherapeutic drugs Behan et al., 2009; Pramanik et al., 2013; Sheng et al., 2017  Sheng et al., 2017  
Secrete glutamine: inhibits the activity of L-asparaginase, a common treatment for ALL Ehsanipour et al., 2013   
Fuel AML blasts survival by production of free fatty acids Shafat et al., 2017; Ye et al., 2016; Li et al., 2018  Shafat et al., 2017  
Lepr+Esm1+ perivascular cells Adipocyte progenitor: negatively regulate HSC function Tikhonova et al., 2019; Naveiras et al., 2009   
Lepr+ cells Following injury, accumulation of adipocytes in the bone marrow: critical for hematopoietic recovery Tikhonova et al., 2019; Zhou et al., 2017   
Immune cells 
T cells CML- and AML-specific T cell responses  Greiner et al., 2006; Molldrem et al., 2000  
Exhaustion contributes to failure of the graft vs. leukemia response in AML patients  Noviello et al., 2019; Toffalori et al., 2019, 
Exhausted subpopulations predict inferior outcome in pediatric B-ALL  Hohtari et al., 2019  
CSF1R-expressing myeloid cells Promote AML growth  Edwards et al., 2019  
Macrophages Promote CLL xenograft survival Galletti et al., 2016   
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