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Role of osteogenic niche in AML progression
opment and response to therapy. Although its fundamen- tal role in HSC maintenance is still debatable, the osteogenic niche stands out as a pivotal sanctuary for LSCs and the cradle of blast production. Putting this into perspective, we foresee that AML-induced genetic changes and osteogenic priming in MSCs illustrate not only the long-standing multiple-hit hypothesis of carcino- genesis but also the newly-coined microenvironment- induced oncogenesis. Importantly, the role of the BM niches in the development of MDS and AML from clonal hematopoiesis of indeterminate potential is still com- pletely unknown.111 Many questions emerge, for instance, regarding the differential role of stage-specific osteolin- eage cells in AML progression, the uncoupling between osteogenesis and osteoclastogenesis, or the net therapeu- tic benefits of LSC dislodgement at the expense of HSC homelessness. Recent advances in our understanding of this osteoblast-rich region in AML progression provide a convincing premise with which to build the next genera-
tion of AML therapy to target the osteogenic niche. However, further studies are needed to clarify the self- reinforcing loop between AML and the osteogenic niche, with the goal of inducing deep remissions and controlling long-termdisease.
Acknowledgements
This work is supported by the Leukemia SPORE career devel- opment award (CA100632), Rolanette and Berdon Lawrence Research Award from Bone Disease Program of Texas, Institutional Research Grant (IRG) from MD Anderson Cancer Center, Cure Sonia Foundation and Golfers Against Cancer Foundation to VLB. In addition, this work was supported by grants from the National Institutes of Health (CA055164) and the MD Anderson Cancer Center Support Grant (CA016672), Cancer Prevention Research Institute of Texas (CPRIT, RP121010), and the Paul and Mary Haas Chair in Genetics to MA. We thank Dr. Marina Konopleva for her valuable sugges- tions in the preparation of this review article.
References
1. MorrisonSJ,ScaddenDT.Thebonemarrow niche for haematopoietic stem cells. Nature. 2014;505(7483):327-334.
2. Itkin T, Gur-Cohen S, Spencer JA, et al. Distinct bone marrow blood vessels differ- entially regulate haematopoiesis. Nature. 2016;532(7599):323-328.
3. Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature. 2014;507(7492):323-328.
4. Langen UH, Pitulescu ME, Kim JM, et al. Cell-matrix signals specify bone endothelial cells during developmental osteogenesis. Nat Cell Biol. 2017;19(3):189-201.
5. Asada N, Takeishi S, Frenette PS. Complexity of bone marrow hematopoietic stem cell niche. Int J Hematol. 2017;106(1):45-54.
6. Miraki-MoudF,Anjos-AfonsoF,HodbyKA, et al. Acute myeloid leukemia does not deplete normal hematopoietic stem cells but induces cytopenias by impeding their differ- entiation. Proc Natl Acad Sci USA. 2013;110(33):13576-13581.
7. Glait-Santar C, Desmond R, Feng X, et al. Functional Niche Competition Between Normal Hematopoietic Stem and Progenitor Cells and Myeloid Leukemia Cells. Stem Cells. 2015;33(12):3635-3642.
8. Krause DS, Fulzele K, Catic A, et al. Differential regulation of myeloid leukemias by the bone marrow microenvironment. Nat Med. 2013;19(11):1513-1517.
9. ZhouHS,CarterBZ,AndreeffM.Bonemar- row niche-mediated survival of leukemia stem cells in acute myeloid leukemia: Yin and Yang. Cancer Biol Med. 2016;13(2):248- 259.
10. Blau O, Hofmann W-K, Baldus CD, et al. Chromosomal aberrations in bone marrow mesenchymal stroma cells from patients with myelodysplastic syndrome and acute myeloblastic leukemia. Exp Hematol. 2007;35(2):221-229.
11. Tabe Y, Shi YX, Zeng Z, et al. TGF-beta- Neutralizing Antibody 1D11 Enhances Cytarabine-Induced Apoptosis in AML Cells
in the Bone Marrow Microenvironment.
PLoS One. 2013;8(6):e62785.
12. Kremer KN, Dudakovic A, McGee-
Lawrence ME, et al. Osteoblasts Protect AML Cells from SDF-1-Induced Apoptosis. J Cell Biochem. 2014;115(6):1128-1137.
13. Ishikawa F, Yoshida S, Saito Y, et al. Chemotherapy-resistant human AML stem cells home to and engraft within the bone- marrow endosteal region. Nat Biotechnol. 2007;25(11):1315-1321.
14. Lord BI, Testa NG, Hendry JH. The relative spatial distributions of CFUs and CFUc in the normal mouse femur. Blood. 1975;46(1):65-72.
15. Lo Celso C, Fleming HE, Wu JW, et al. Live- animal tracking of individual haematopoiet- ic stem/progenitor cells in their niche. Nature. 2009;457(7225):92-96.
16. Taichman RS, Emerson SG. Human osteoblasts support hematopoiesis through the production of granulocyte colony-stimu- lating factor. J Exp Med. 1994;179(5):1677- 1682.
17. Taichman RS, Reilly MJ, Verma RS, Ehrenman K, Emerson SG. Hepatocyte growth factor is secreted by osteoblasts and cooperatively permits the survival of haematopoietic progenitors. Br J Haematol. 2001;112(2):438-448.
18. Stier S, Ko Y, Forkert R, et al. Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size. J Exp Med. 2005;201(11):1781-1791.
19. Sugiyama T, Kohara H, Noda M, Nagasawa T. Maintenance of the Hematopoietic Stem Cell Pool by CXCL12-CXCR4 Chemokine Signaling in Bone Marrow Stromal Cell Niches. Immunity. 2006;25(6):977-988.
20. Ulyanova T, Scott LM, Priestley GV, et al. VCAM-1 expression in adult hematopoietic and nonhematopoietic cells is controlled by tissue-inductive signals and reflects their developmental origin. Blood. 2005;106(1): 86-94.
21. Katayama Y, Battista M, Kao WM, et al. Signals from the sympathetic nervous sys- tem regulate hematopoietic stem cell egress from bone marrow. Cell. 2006;124(2):407- 421.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and con- trol of the niche size. Nature. 2003;425(6960):836-841.
Calvi LM, Adams GB, Weibrecht KW, et al. Osteoblastic cells regulate the haematopoi- etic stem cell niche. Nature. 2003;425 (6960):841-846.
Arai F, Hirao A, Ohmura M, et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell. 2004;118(2):149- 161.
Yoshihara H, Arai F, Hosokawa K, et al. Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Cell Stem Cell. 2007;1(6):685-697.
Fleming HE, Janzen V, Celso CL, et al. Wnt signaling in the niche enforces hematopoiet- ic stem cell quiescence and is necessary to preserve self-renewal in vivo. Cell Stem Cell. 2008;2(3):274-283.
Bowers M, Zhang B, Ho Y, et al. Osteoblast ablation reduces normal long-term hematopoietic stem cell self-renewal but accelerates leukemia development. Blood. 2015;125(17):2678-2688.
Ma YD, Park C, Zhao H, et al. Defects in osteoblast function but no changes in long- term repopulating potential of hematopoiet- ic stem cells in a mouse chronic inflammato- ry arthritis model. Blood. 2009;114(20):4402- 4410.
Greenbaum A, Hsu Y-MS, Day RB, et al. CXCL12 Production by Early Mesenchymal Progenitors is Required for Hematopoietic Stem Cell Maintenance. Nature. 2013;495(7440):227-230.
Ding L, Saunders TL, Enikolopov G, Morrison SJ. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature. 2012;481(7382):457-462.
Nakamura Y, Arai F, Iwasaki H, et al. Isolation and characterization of endosteal niche cell populations that regulate hematopoietic stem cells. Blood. 2010;116 (9):1422-1432.
Walter MJ, Shen D, Ding L, et al. Clonal Architecture of Secondary Acute Myeloid
haematologica | 2018; 103(12)
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