| Niche component . | Function/role . | Mouse studies . | Human 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 | |
| Niche component . | Function/role . | Mouse studies . | Human 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 | |