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The Osteoblastic Niche in Hematopoiesis and Hematological Myeloid Malignancies

  • Molecular Biology of Skeletal Development (T Bellido, Section Editor)
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Abstract

Purpose of Review

This review focuses on evidence highlighting the bidirectional crosstalk between the hematopoietic stem cell (HSC) and their surrounding stromal cells, with a particular emphasis on cells of the osteoblast lineage. The role and molecular functions of osteoblasts in normal hematopoiesis and in myeloid hematological malignancies is discussed.

Recent Findings

Cells of the osteoblast lineage have emerged as potent regulators of HSC expansion that regulate their recruitment and, depending on their stage of differentiation, their activity, proliferation, and differentiation along the lymphoid, myeloid, and erythroid lineages. In addition, mutations in mature osteoblasts or their progenitors induce myeloid malignancies. Conversely, signals from myelodysplastic cells can remodel the osteoblastic niche to favor self-perpetuation.

Summary

Understanding cellular crosstalk between osteoblastic cells and HSCs in the bone marrow microenvironment is of fundamental importance for developing therapies against benign and malignant hematological diseases.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Jacobson LO, Simmons EL, Marks EK, Eldredge JH. Recovery from Radiation Injury. Science. American Association for the Advancement of Science; 1951;113:510–1.

  2. McCulloch EA, Till JE. The radiation sensitivity of normal mouse bone marrow cells, determined by quantitative marrow transplantation into irradiated mice. Radiat Res. 1960;13:115–25.

    Article  CAS  PubMed  Google Scholar 

  3. Yamamoto R, Morita Y, Ooehara J, Hamanaka S, Onodera M, Rudolph KL, et al. Clonal analysis unveils self-renewing lineage-restricted progenitors generated directly from hematopoietic stem cells. Cell. 2013;154:1112–26.

    Article  CAS  PubMed  Google Scholar 

  4. Spangrude GJ, Heimfeld S, Weissman IL. Purification and characterization of mouse hematopoietic stem cells. Science. 1988;241:58–62.

    Article  CAS  PubMed  Google Scholar 

  5. Yang L. Identification of Lin-Sca1+kit+CD34+Flt3- short-term hematopoietic stem cells capable of rapidly reconstituting and rescuing myeloablated transplant recipients. Blood. 2005;105:2717–23.

    Article  CAS  PubMed  Google Scholar 

  6. Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells. 1978;4:7–25.

    CAS  PubMed  Google Scholar 

  7. Sauvageau G, Iscove NN, Humphries RK. In vitro and in vivo expansion of hematopoietic stem cells. Oncogene. 2004;23:7223–32.

    Article  CAS  PubMed  Google Scholar 

  8. Bodine DM, Karlsson S, Nienhuis AW. Combination of interleukins 3 and 6 preserves stem cell function in culture and enhances retrovirus-mediated gene transfer into hematopoietic stem cells. Proc Natl Acad Sci. 1989;86:8897–901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ku H, Yonemura Y, Kaushansky K, Ogawa M. Thrombopoietin, the ligand for the Mpl receptor, synergizes with steel factor and other early acting cytokines in supporting proliferation of primitive hematopoietic progenitors of mice. Blood. 1996;87:4544–51.

    CAS  PubMed  Google Scholar 

  10. Matsunaga T, Kato T, Miyazaki H, Ogawa M. Thrombopoietin promotes the survival of murine hematopoietic long-term reconstituting cells: comparison with the effects of FLT3/FLK-2 ligand and interleukin-6. Blood. 1998;92:452–61.

    CAS  PubMed  Google Scholar 

  11. Miller CL, Eaves CJ. Expansion in vitro of adult murine hematopoietic stem cells with transplantable lympho-myeloid reconstituting ability. Proc Natl Acad Sci. 1997;94:13648–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ema H, Takano H, Sudo K, Nakauchi H. In vitro self-renewal division of hematopoietic stem cells. J Exp Med. 2000;192:1281–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Himburg HA, Muramoto GG, Daher P, Meadows SK, Russell JL, Doan P, et al. Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells. Nat Med. 2010;16:475–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhang CC, Kaba M, Ge G, Xie K, Tong W, Hug C, et al. Angiopoietin-like proteins stimulate ex vivo expansion of hematopoietic stem cells. Nat Med. 2006;12:240–5.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Zhang CC, Lodish HF. Insulin-like growth factor 2 expressed in a novel fetal liver cell population is a growth factor for hematopoietic stem cells. Blood. 2004;103:2513–21.

    Article  CAS  PubMed  Google Scholar 

  16. de Haan G, Weersing E, Dontje B, van Os R, Bystrykh LV, Vellenga E, et al. In vitro generation of long-term repopulating hematopoietic stem cells by fibroblast growth factor-1. Dev Cell. 2003;4:241–51.

    Article  PubMed  Google Scholar 

  17. Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature. 2014;505:327–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Raaijmakers MHGP, Mukherjee S, Guo S, Zhang S, Kobayashi T, Schoonmaker JA, et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. 2010;464:852–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Walkley CR, Olsen GH, Dworkin S, Fabb SA, Swann J, McArthur GA, et al. A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor γ deficiency. Cell. 2007;129:1097–110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. •• Kode A, Manavalan JS, Mosialou I, Bhagat G, Rathinam CV, Luo N, et al. Leukaemogenesis induced by an activating β-catenin mutation in osteoblasts. Nature. 2014;506:240–4. This study showed for the first time that a mutation in osteoblasts leads to MDS rapidly progressing to AML with clonal cytogenetic abnormalities. The leukemogenic pathway is active in a subpopulation of MDS and AML patients .

  21. • Krevvata M, Silva BC, Manavalan JS, Galán-Díez M, Kode A, Matthews BG, et al. Inhibition of leukemia cell engraftment and disease progression in mice by osteoblasts. Blood. 2014;124:2834–46. This paper indicates that osteoblast numbers are compromised in patients with MDS and AML and osteoblasts are protective against AML engraftment and progression in mice .

  22. Gong JK. Endosteal marrow: a rich source of hematopoietic stem cells. Science. 1978;199:1443–5.

    Article  CAS  PubMed  Google Scholar 

  23. Taichman RS, Emerson SG. Human osteoblasts support hematopoiesis through the production of granulocyte colony-stimulating factor. The Journal of Experimental Medicine. Rockefeller University Press; 1994;179:1677–82.

  24. Lord BI, Testa NG, Hendry JH. The relative spatial distributions of CFUs and CFUc in the normal mouse femur. Blood. 1975;46:65–72.

    CAS  PubMed  Google Scholar 

  25. El-Badri N, Wang BY, Cherry, Good RA. Osteoblasts promote engraftment of allogeneic hematopoietic stem cells. Exp Hematol. 1998;26:110–6.

    CAS  PubMed  Google Scholar 

  26. Miyamoto K, Yoshida S, Kawasumi M, Hashimoto K, Kimura T, Sato Y, et al. Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization. J Exp Med. 2011;208:2175–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425:836–41.

    Article  Google Scholar 

  28. Zhang J, Niu C, Ye L, Huang H, He X, Tong W-G, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425:832–6.

    Article  Google Scholar 

  29. Nilsson SK. Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood. 2005;106:1232–9.

    Article  CAS  PubMed  Google Scholar 

  30. Stier S, Ko Y, Forkert R, Lutz C, Neuhaus T, Grünewald E, et al. Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size. J Exp Med. 2005;201:1781–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Bowers M, Zhang B, Ho Y, Agarwal P, Chen C-C, Bhatia R. Osteoblast ablation reduces normal long-term hematopoietic stem cell self-renewal but accelerates leukemia development. Blood American Society of Hematology. 2015;125:2678–88.

    CAS  Google Scholar 

  32. Beate Heissig, Koichi Hattori, Dias S, Friedrich M, Barbara Ferris, Hackett NR, et al. Recruitment of Stem and Progenitor Cells from the Bone Marrow Niche Requires MMP-9 Mediated Release of Kit-Ligand. Cell. 2002:1–22.

  33. Nilsson SK, Johnston HM, Coverdale JA. Spatial localization of transplanted hemopoietic stem cells: inferences for the localization of stem cell niches. Blood. 2001;97:2293–9.

    Article  CAS  PubMed  Google Scholar 

  34. Celso Lo C, Fleming HE, Wu JW, Zhao CX, Miake-Lye S, Fujisaki J, et al. Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche. Nature. 2009;457:92–6.

  35. Xie Y, Yin T, Wiegraebe W, He XC, Miller D, Stark D, et al. Detection of functional haematopoietic stem cell niche using real-time imaging. Nature. 2009;457:97–101.

  36. Zhang J, Niu C, Ye L, Huang H, He X, Tong W-G, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425:836–41.

    Article  CAS  PubMed  Google Scholar 

  37. Kim S, Lin L, Brown GAJ, Hosaka K, Scott EW. Extended time-lapse in vivo imaging of tibia bone marrow to visualize dynamic hematopoietic stem cell engraftment. Leukemia. 2017.

  38. Grassinger J, Haylock DN, Williams B, Olsen GH, Nilsson SK. Phenotypically identical hemopoietic stem cells isolated from different regions of bone marrow have different biologic potential. Blood. 2010;116:3185–96.

  39. Haylock DN, Williams B, Johnston HM, Liu MCP, Rutherford KE, Whitty GA, et al. Hemopoietic stem cells with higher hemopoietic potential reside at the bone marrow endosteum. Stem Cells. 2007;25:1062–9.

    Article  CAS  PubMed  Google Scholar 

  40. • Acar M, Kocherlakota KS, Murphy MM, Peyer JG, Oguro H, Inra CN, et al. Deep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal. Nature. 2015;526:126–30. This study shows that quiescent HSC are more associated with BM sinusoids rather than arterioles and that, Leptin receptor expressing cells play and important role in HSC quiescence maintenance.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. •• Chen JY, Miyanishi M, Wang SK, Yamazaki S, Sinha R, Kao KS, et al. Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche. Nature. 2016;530:223–7. This paper identifies a unique marker to mark LT-HSCs, the HSCs that replicate indefinitely and are critical to lifelong blood production.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tokoyoda K, Egawa T, Sugiyama T, Choi B-I, Nagasawa T. Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity. 2004;20:707–18.

    Article  CAS  PubMed  Google Scholar 

  43. Zhu J, Garrett R, Jung Y, Zhang Y, Kim N, Wang J, et al. Osteoblasts support B-lymphocyte commitment and differentiation from hematopoietic stem cells. Blood. 2007;109:3706–12.

    Article  CAS  PubMed  Google Scholar 

  44. Visnjic D, Kalajzic Z, Rowe DW, Katavic V, Lorenzo J, Aguila HL. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood. 2004;103:3258–64.

    Article  CAS  PubMed  Google Scholar 

  45. Wu JY, Purton LE, Rodda SJ, Chen M, Weinstein LS, McMahon AP, et al. Osteoblastic regulation of B lymphopoiesis is mediated by Gsa-dependent signaling pathways. Proceedings of the National Academy of Sciences; 2008;105:16976–81.

  46. Day RB, Bhattacharya D, Nagasawa T, Link DC. Granulocyte colony-stimulating factor reprograms bone marrow stromal cells to actively suppress B lymphopoiesis in mice. Blood; 2015;125:3114–7.

  47. Morad V, Pevsner-Fischer M, Barnees S, Samokovlisky A, Rousso-Noori L, Rosenfeld R, et al. The myelopoietic supportive capacity of mesenchymal stromal cells is uncoupled from multipotency and is influenced by lineage determination and interference with glycosylation. Stem Cells. 2008;26:2275–86.

  48. Sacchetti B, Funari A, Michienzi S, Di Cesare S, Piersanti S, Saggio I, et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell. 2007;131:324–36.

    Article  CAS  PubMed  Google Scholar 

  49. He Q, Scott Swindle C, Wan C, Flynn RJ, Oster RA, Chen D, et al. Enhanced hematopoietic stem cell self-renewal-promoting ability of clonal primary mesenchymal stromal/stem cells versus their osteogenic progeny. Stem Cells. 2017;35:473–84.

    Article  CAS  PubMed  Google Scholar 

  50. Méndez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA, et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010;466:829–34.

  51. Calvi LM, Bromberg O, Rhee Y, Weber JM, Smith JNP, Basil MJ, et al. Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells. Blood. 2012;119:2489–99.

  52. • Kunisaki Y, Bruns I, Scheiermann C, Ahmed J, Pinho S, Zhang D, et al. Arteriolar niches maintain haematopoietic stem cell quiescence. Nature. 2013;502:637–43. This paper characterizes histologically the different vascular structure subtypes and show that the peri-arteriolar mesenchymal cells control HSC maintenance.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Arai F, Hirao A, Ohmura M, Sato H, Matsuoka S, Takubo K, et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell. 2004;118:149–61.

    Article  CAS  PubMed  Google Scholar 

  54. Yoshihara H, Arai F, Hosokawa K, Hagiwara T, Takubo K, Nakamura Y, et al. Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Cell Stem Cell. 2007;1:685–97.

    Article  CAS  PubMed  Google Scholar 

  55. Jung Y, Wang J, Song J, Shiozawa Y, Wang J, Wang J, et al. Annexin II expressed by osteoblasts and endothelial cells regulates stem cell adhesion, homing, and engraftment following transplantation. Blood. 2007;110:82–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ponomaryov T, Peled A, Petit I, Taichman RS, Habler L, Sandbank J, et al. Induction of the chemokine stromal-derived factor-1 following DNA damage improves human stem cell function. J Clin Invest. 2000;106:1331–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Weber JM, Forsythe SR, Christianson CA, Frisch BJ, Gigliotti BJ, Jordan CT, et al. Parathyroid hormone stimulates expression of the notch ligand Jagged1 in osteoblastic cells. Bone. 2006;39:485–93.

    Article  CAS  PubMed  Google Scholar 

  58. Milner LA, Bigas A. Notch as a mediator of cell fate determination in hematopoiesis: evidence and speculation. Blood. 1999;93:2431–48.

    CAS  PubMed  Google Scholar 

  59. Karanu FN, Murdoch B, Gallacher L, Wu DM, Koremoto M, Sakano S, et al. The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells. J Exp Med. 2000;192:1365–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kode A, Mosialou I, Manavalan SJ, Rathinam CV, Friedman RA, Teruya-Feldstein J, et al. FoxO1-dependent induction of acute myeloid leukemia by osteoblasts in mice. Leukemia. 2016;30:1–13.

    Article  CAS  PubMed  Google Scholar 

  61. Chitteti BR, Cheng Y-H, Poteat B, Rodriguez-Rodriguez S, Goebel WS, Carlesso N, et al. Impact of interactions of cellular components of the bone marrow microenvironment on hematopoietic stem and progenitor cell function. Blood. American Society of Hematology; 2010;115:3239–48.

  62. Maillard I, Koch U, Dumortier A, Shestova O, Xu L, Sai H, et al. Canonical notch signaling is dispensable for the maintenance of adult hematopoietic stem cells. Cell Stem Cell. 2008;2:356–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ding L, Saunders TL, Enikolopov G, Morrison SJ. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature. 2012;481:457–62.

  64. Grassinger J, Haylock DN, Storan MJ, Haines GO, Williams B, Whitty GA, et al. Thrombin-cleaved osteopontin regulates hemopoietic stem and progenitor cell functions through interactions with alpha9beta1 and alpha4beta1 integrins. Blood. 2009;114:49–59.

    Article  CAS  PubMed  Google Scholar 

  65. Puri MC, Bernstein A. Requirement for the TIE family of receptor tyrosine kinases in adult but not fetal hematopoiesis. Proceedings of the National Academy of Sciences. 2003;100:12753–8.

  66. Frisch BJ, Porter RL, Gigliotti BJ, Olm-Shipman AJ, Weber JM, O'Keefe RJ, et al. In vivo prostaglandin E2 treatment alters the bone marrow microenvironment and preferentially expands short-term hematopoietic stem cells. Blood. 2009;114:4054–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. North TE, Goessling W, Walkley CR, Lengerke C, Kopani KR, Lord AM, et al. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature. 2007;447:1007–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Goessling W, Allen RS, Guan X, Jin P, Uchida N, Dovey M, et al. Prostaglandin E2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models. Cell Stem Cell. 2011;8:445–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Hoggatt J, Singh P, Sampath J, Pelus LM. Prostaglandin E2 enhances hematopoietic stem cell homing, survival, and proliferation. Blood. 2009;113:5444–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Hoggatt J, Mohammad KS, Singh P, Hoggatt AF, Chitteti BR, Speth JM, et al. Differential stem- and progenitor-cell trafficking by prostaglandin E2. Nature. 2013;495:365–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Porter RL, Georger MA, Bromberg O, McGrath KE, Frisch BJ, Becker MW, et al. Prostaglandin E2 increases hematopoietic stem cell survival and accelerates hematopoietic recovery after radiation injury. Stem Cells. 2013;31:372–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Spencer JA, Ferraro F, Roussakis E, Klein A, Wu J, Runnels JM, et al. Direct measurement of local oxygen concentration in the bone marrow of live animals. Nature. 2014;508:269–73.

  73. Takubo K, Goda N, Yamada W, Iriuchishima H, Ikeda E, Kubota Y, et al. Regulation of the HIF-1alpha level is essential for hematopoietic stem cells. Cell Stem Cell. 2010;7:391–402.

    Article  CAS  PubMed  Google Scholar 

  74. Pollard PJ, Kranc KR. Hypoxia signaling in hematopoietic stem cells: a double-edged sword. Cell Stem Cell. 2010;7:276–8.

    Article  CAS  PubMed  Google Scholar 

  75. Adams GB, Chabner KT, Alley IR, Olson DP, Szczepiorkowski ZM, Poznansky MC, et al. Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature. 2006;439:599–603.

    Article  CAS  PubMed  Google Scholar 

  76. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 1997;89:747–54.

    Article  CAS  PubMed  Google Scholar 

  77. Lee B, Thirunavukkarasu K, Zhou L, Pastore L, Baldini A, Hecht J, et al. Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia. Nat Genet. 1997;16:307–10.

    Article  CAS  PubMed  Google Scholar 

  78. •• Greenbaum A, Hsu Y-MS, Day RB, Schuettpelz LG, Christopher MJ, Borgerding JN, et al. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature. 2013;495:227–30. This study performed a systematic analysis of the BM-CXCL12-expressing, demonstrating the specific role of MSCs and endothelial cells in regulating HSC maintenance .

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. •• Ding L, Morrison SJ. Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature. 2013;495:231–5. This paper is another systematic analysis of CXCL12-expressing cells in the BM and demonstrated that HSC and restricted progenitors depend on distinct cellular niches .

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. • Luo Y, Chen G-L, Hannemann N, Ipseiz N, Krönke G, Bäuerle T, et al. Microbiota from obese mice regulate hematopoietic stem cell differentiation by altering the bone niche. Cell Metab. 2015;22:886–94. This paper shows that altering gut microbiota by feeding the mice a high fat diet can disrupt HSC quiescence by influencing the HSC niche through altering stromal cell populations, increasing MSC differentiation towards adipocytes rather than osteoblasts .

    Article  CAS  PubMed  Google Scholar 

  81. Joseph C, Quach JM, Walkley CR, Lane SW, Celso Lo C, Purton LE. Deciphering hematopoietic stem cells in their niches: a critical appraisal of genetic models, lineage tracing, and imaging strategies. Cell Stem Cell. 2013;13:520–33.

    Article  CAS  PubMed  Google Scholar 

  82. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.

    Article  CAS  PubMed  Google Scholar 

  83. Hope KJ, Jin L, Dick JE. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol. 2004;5:738–43.

    Article  CAS  PubMed  Google Scholar 

  84. Scadden DT. Cancer stem cells refined. Nat Immunol. 2004;5:701–3.

    Article  CAS  PubMed  Google Scholar 

  85. Passegué E, Jamieson CHM, Ailles LE, Weissman IL. Normal and leukemic hematopoiesis: are leukemias a stem cell disorder or a reacquisition of stem cell characteristics? Proceedings of the National Academy of Sciences. 2003;100 Suppl 1:11842–9.

  86. Frisch BJ, Ashton JM, Xing L, Becker MW, Jordan CT, Calvi LM. Functional inhibition of osteoblastic cells in an in vivo mouse model of myeloid leukemia. Blood. 2012;119:540–50.

  87. •• Schepers K, Pietras EM, Reynaud D, Flach J, Binnewies M, Garg T, et al. Myeloproliferative Neoplasia Remodels the Endosteal Bone Marrow Niche into a Self-Reinforcing Leukemic Niche. Stem Cell. Elsevier Inc; 2013;13:285–99. This study demonstrated that dysplastic myeloproliferative cells can reprogram osteoblast in the endosteal niche to favor self-perpetuation .

  88. Tu X, Delgado-Calle J, Condon KW, Maycas M, Zhang H, Carlesso N, et al. Osteocytes mediate the anabolic actions of canonical Wnt/β-catenin signaling in bone. Proc Natl Acad Sci. 2015;112:E478–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. •• Dong L, Yu W-M, Zheng H, Loh ML, Bunting ST, Pauly M, et al. Leukaemogenic effects of Ptpn11 activating mutations in the stem cell microenvironment. Nature. 2016;539:304–8. This study identifies a mutation in the Nestin-expressing stromal niche that can lead to leukemia.

  90. Zambetti NA, Ping Z, Chen S, Kenswil KJG, Mylona MA, Sanders MA, et al. Mesenchymal inflammation drives genotoxic stress in hematopoietic stem cells and predicts disease evolution in human pre-leukemia. Cell Stem Cell. 2016;19:613–27.

    Article  CAS  PubMed  Google Scholar 

  91. Colmone A, Amorim M, Pontier AL, Wang S, Jablonski E, Sipkins DA. Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells. Science. 2008;322:1861–5.

    Article  CAS  PubMed  Google Scholar 

  92. Glait-Santar C, Desmond R, Feng X, Bat T, Chen J, Heuston E, et al. Functional niche competition between normal hematopoietic stem and progenitor cells and myeloid leukemia cells. Stem Cells. 2015;33:3635–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Lane SW, Wang YJ, Celso Lo C, Ragu C, Bullinger L, Sykes SM, et al. Differential niche and Wnt requirements during acute myeloid leukemia progression. Blood. 2011;118:2849–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Ishikawa F, Yoshida S, Saito Y, Hijikata A, Kitamura H, Tanaka S, et al. Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nat Biotechnol. 2007;25:1315–21.

    Article  CAS  PubMed  Google Scholar 

  95. Nervi B, Ramirez P, Rettig MP, Uy GL, Holt MS, Ritchey JK, et al. Chemosensitization of acute myeloid leukemia (AML) following mobilization by the CXCR4 antagonist AMD3100. Blood. 2009;113:6206–14.

  96. Zeng Z, Shi YX, Samudio IJ, Wang R-Y, Ling X, Frolova O, et al. Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML. Blood. 2009;113:6215–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. •• Duan C-W, Shi J, Chen J, Wang B, Yu Y-H, Qin X, et al. Leukemia propagating cells rebuild an evolving niche in response to therapy. Cancer Cell. 2014;25:778–93. This study highlights the role of the leukemia stromal niche in resistance to therapy and its regulation by leukemic cells .

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Physiology & Cellular Biophysics, College of Physicians & Surgeons, Columbia University, New York, NY, 10032, USA

    Marta Galán-Díez & Stavroula Kousteni

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  1. Marta Galán-Díez
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This article is part of the Topical Collection on Molecular Biology of Skeletal Development

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Galán-Díez, M., Kousteni, S. The Osteoblastic Niche in Hematopoiesis and Hematological Myeloid Malignancies. Curr Mol Bio Rep 3, 53–62 (2017). https://doi.org/10.1007/s40610-017-0055-9

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