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Cited by 238Multiple Myeloma Research and TreatmentsChronic Lymphocytic Leukemia ResearchBone health and treatments

The Role of Tumor Microenvironment in Multiple Myeloma Development and Progression

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García-Ortiz, Almudena, Rodríguez-García, Yaiza, Encinas, Jessica, Maroto-Martín, Elena, Castellano, Eva, Teixidó, Joaquín, Martínez-López, Joaquín·2021·Cancers
DOI 10.3390/cancers13020217PMC PMC7827690
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Abstract

Multiple myeloma (MM) is a hematologic cancer characterized by clonal proliferation of plasma cells in the bone marrow (BM). The progression, from the early stages of the disease as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to MM and occasionally extramedullary disease, is drastically affected by the tumor microenvironment (TME). Soluble factors and direct cell–cell interactions regulate MM plasma cell trafficking and homing to the BM niche. Mesenchymal stromal cells, osteoclasts, osteoblasts, myeloid and lymphoid cells present in the BM create a unique milieu that favors MM plasma cell immune evasion and promotes disease progression. Moreover, TME is implicated in malignant cell protection against anti-tumor therapy. This review describes the main cellular and non-cellular components located in the BM, which condition the immunosuppressive environment and lead the MM establishment and progression.

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  • Multiple myeloma cells may function remotely to create new premetastatic niches for tumor spread in other bone areas by secreting growth factors, cytokines, and exosomes that alter the extracellular matrix in these new locations.

    “Moreover, as previously indicated, MM cells may now function remotely to create new premetastatic niches for tumor spread in other bone areas by secreting growth factors, cytokines, and exosomes that alter the ECM in these new locations [291].”

    From Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword (2025) · cites this paper as [291]

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  1. [1]Siegel R.L. Miller K.D. Jemal A. Cancer statistics, 2019 CA A Cancer J. Clin. 2019 69 7 34 10.3322/caac.21551 30620402 · DOI · Paper page
  2. [2]Kumar S.K. Rajkumar V. Kyle R.A. van Duin M. Sonneveld P. Mateos M.V. Gay F. Anderson K.C. Multiple myeloma Nat. Rev. Dis. Primers 2017 3 17046 10.1038/nrdp.2017.46 28726797 · DOI
  3. [3]Redondo-Munoz J. Garcia-Pardo A. Teixido J. Molecular Players in Hematologic Tumor Cell Trafficking Front Immunol. 2019 10 156 10.3389/fimmu.2019.00156 30787933 PMC6372527 · DOI
  4. [4]Ghobrial I.M. Myeloma as a model for the process of metastasis: Implications for therapy Blood 2012 120 20 30 10.1182/blood-2012-01-379024 22535658 PMC3390959 · DOI
  5. [5]Chu V.T. Berek C. The establishment of the plasma cell survival niche in the bone marrow Immunol. Rev. 2013 251 177 188 10.1111/imr.12011 23278749 · DOI
  6. [6]Méndez-Ferrer S. Bonnet D. Steensma D.P. Hasserjian R.P. Ghobrial I.M. Gribben J.G. Andreeff M. Krause D.S. Bone marrow niches in haematological malignancies Nat. Rev. Cancer 2020 20 285 298 10.1038/s41568-020-0245-2 32112045 PMC9912977 · DOI
  7. [7]Ghobrial I.M. Detappe A. Anderson K.C. Steensma D.P. The bone-marrow niche in MDS and MGUS: Implications for AML and MM Nat. Rev. Clin. Oncol. 2018 15 219 233 10.1038/nrclinonc.2017.197 29311715 · DOI
  8. [8]Lindquist R.L. Niesner R.A. Hauser A.E. In the Right Place, at the Right Time: Spatiotemporal Conditions Determining Plasma Cell Survival and Function Front Immunol. 2019 10 788 10.3389/fimmu.2019.00788 31068930 PMC6491733 · DOI
  9. [9]Hargreaves D.C. Hyman P.L. Lu T.T. Ngo V.N. Bidgol A. Suzuki G. Zou Y.R. Littman D.R. Cyster J.G. A coordinated change in chemokine responsiveness guides plasma cell movements J. Exp. Med. 2001 194 45 56 10.1084/jem.194.1.45 11435471 PMC2193440 · DOI
  10. [10]Tokoyoda K. Egawa T. Sugiyama T. Choi B.I. Nagasawa T. Cellular niches controlling B lymphocyte behavior within bone marrow during development Immunity 2004 20 707 718 10.1016/j.immuni.2004.05.001 15189736 · DOI
  11. [11]Nie Y. Waite J. Brewer F. Sunshine M.J. Littman D.R. Zou Y.R. The role of CXCR4 in maintaining peripheral B cell compartments and humoral immunity J. Exp. Med. 2004 200 1145 1156 10.1084/jem.20041185 15520246 PMC2211858 · DOI
  12. [12]Moller C. Stromberg T. Juremalm M. Nilsson K. Nilsson G. Expression and function of chemokine receptors in human multiple myeloma Leukemia 2003 17 203 210 10.1038/sj.leu.2402717 12529679 · DOI
  13. [13]Alsayed Y. Ngo H. Runnels J. Leleu X. Singha U.K. Pitsillides C.M. Spencer J.A. Kimlinger T. Ghobrial J.M. Jia X. Mechanisms of regulation of CXCR4/SDF-1 (CXCL12)-dependent migration and homing in multiple myeloma Blood 2007 109 2708 2717 10.1182/blood-2006-07-035857 17119115 PMC1852222 · DOI
  14. [14]Azab A.K. Runnels J.M. Pitsillides C. Moreau A.S. Azab F. Leleu X. Jia X. Wright R. Ospina B. Carlson A.L. CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy Blood 2009 113 4341 4351 10.1182/blood-2008-10-186668 19139079 PMC2676090 · DOI
  15. [15]Sanz-Rodriguez F. Hidalgo A. Teixido J. Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1/fibronectin and VCAM-1 Blood 2001 97 346 351 10.1182/blood.V97.2.346 11154207 · DOI
  16. [16]Martinez-Moreno M. Leiva M. Aguilera-Montilla N. Sevilla-Movilla S. Isern de Val S. Arellano-Sanchez N. Gutierrez N.C. Maldonado R. Martinez-Lopez J. Buno I. In vivo adhesion of malignant B cells to bone marrow microvasculature is regulated by alpha4beta1 cytoplasmic-binding proteins Leukemia 2016 30 861 872 10.1038/leu.2015.332 26658839 · DOI
  17. [17]Wright N. de Lera T.L. Garcia-Moruja C. Lillo R. Garcia-Sanchez F. Caruz A. Teixido J. Transforming growth factor-beta1 down-regulates expression of chemokine stromal cell-derived factor-1: Functional consequences in cell migration and adhesion Blood 2003 102 1978 1984 10.1182/blood-2002-10-3190 12775566 · DOI
  18. [18]Neri P. Ren L. Azab A.K. Brentnall M. Gratton K. Klimowicz A.C. Lin C. Duggan P. Tassone P. Mansoor A. Integrin β7-mediated regulation of multiple myeloma cell adhesion, migration, and invasion Blood 2011 117 6202 6213 10.1182/blood-2010-06-292243 21474670 PMC3122944 · DOI
  19. [19]Hurt E.M. Wiestner A. Rosenwald A. Shaffer A.L. Campo E. Grogan T. Bergsagel P.L. Kuehl W.M. Staudt L.M. Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma Cancer Cell 2004 5 191 199 10.1016/S1535-6108(04)00019-4 14998494 · DOI
  20. [20]Asosingh K. Gunthert U. De Raeve H. Van Riet I. Van Camp B. Vanderkerken K. A unique pathway in the homing of murine multiple myeloma cells: CD44v10 mediates binding to bone marrow endothelium Cancer Res. 2001 61 2862 2865 11306459
  21. [21]Snapp K.R. Ding H. Atkins K. Warnke R. Luscinskas F.W. Kansas G.S. A novel P-selectin glycoprotein ligand-1 monoclonal antibody recognizes an epitope within the tyrosine sulfate motif of human PSGL-1 and blocks recognition of both P- and L-selectin Blood 1998 91 154 164 10.1182/blood.V91.1.154 9414280 · DOI
  22. [22]Azab A.K. Quang P. Azab F. Pitsillides C. Thompson B. Chonghaile T. Patton J.T. Maiso P. Monrose V. Sacco A. P-selectin glycoprotein ligand regulates the interaction of multiple myeloma cells with the bone marrow microenvironment Blood 2012 119 1468 1478 10.1182/blood-2011-07-368050 22096244 PMC3286211 · DOI
  23. [23]Glavey S.V. Manier S. Natoni A. Sacco A. Moschetta M. Reagan M.R. Murillo L.S. Sahin I. Wu P. Mishima Y. The sialyltransferase ST3GAL6 influences homing and survival in multiple myeloma Blood 2014 124 1765 1776 10.1182/blood-2014-03-560862 25061176 PMC4162107 · DOI
  24. [24]Natoni A. Farrell M.L. Harris S. Falank C. Kirkham-McCarthy L. Macauley M.S. Reagan M.R. O’Dwyer M. Sialyltransferase inhibition leads to inhibition of tumor cell interactions with E-selectin, VCAM1, and MADCAM1, and improves survival in a human multiple myeloma mouse model Haematologica 2020 105 457 467 10.3324/haematol.2018.212266 31101754 PMC7012485 · DOI
  25. [25]Lokhorst H.M. Lamme T. de Smet M. Klein S. de Weger R.A. van Oers R. Bloem A.C. Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures Blood 1994 84 2269 2277 10.1182/blood.V84.7.2269.2269 7919345 · DOI
  26. [26]Sanz-Rodriguez F. Ruiz-Velasco N. Pascual-Salcedo D. Teixido J. Characterization of VLA-4-dependent myeloma cell adhesion to fibronectin and VCAM-1 Br. J. Haematol. 1999 107 825 834 10.1046/j.1365-2141.1999.01762.x 10606891 · DOI
  27. [27]Michigami T. Shimizu N. Williams P.J. Niewolna M. Dallas S.L. Mundy G.R. Yoneda T. Cell-cell contact between marrow stromal cells and myeloma cells via VCAM-1 and alpha(4)beta(1)-integrin enhances production of osteoclast-stimulating activity Blood 2000 96 1953 1960 10.1182/blood.V96.5.1953 10961900 · DOI
  28. [28]Podar K. Zimmerhackl A. Fulciniti M. Tonon G. Hainz U. Tai Y.T. Vallet S. Halama N. Jager D. Olson D.L. The selective adhesion molecule inhibitor Natalizumab decreases multiple myeloma cell growth in the bone marrow microenvironment: Therapeutic implications Br. J. Haematol. 2011 155 438 448 10.1111/j.1365-2141.2011.08864.x 21923653 · DOI
  29. [29]Mori Y. Shimizu N. Dallas M. Niewolna M. Story B. Williams P.J. Mundy G.R. Yoneda T. Anti-alpha4 integrin antibody suppresses the development of multiple myeloma and associated osteoclastic osteolysis Blood 2004 104 2149 2154 10.1182/blood-2004-01-0236 15138161 · DOI
  30. [30]Olson D.L. Burkly L.C. Leone D.R. Dolinski B.M. Lobb R.R. Anti-alpha4 integrin monoclonal antibody inhibits multiple myeloma growth in a murine model Mol. Cancer Ther. 2005 4 91 99 15657357
  31. [31]Anderson K.C. Carrasco R.D. Pathogenesis of myeloma Annu. Rev. Pathol. 2011 6 249 274 10.1146/annurev-pathol-011110-130249 21261519 · DOI
  32. [32]Bianchi G. Munshi N.C. Pathogenesis beyond the cancer clone(s) in multiple myeloma Blood 2015 125 3049 3058 10.1182/blood-2014-11-568881 25838343 PMC4432002 · DOI
  33. [33]Damiano J.S. Cress A.E. Hazlehurst L.A. Shtil A.A. Dalton W.S. Cell adhesion mediated drug resistance (CAM-DR): Role of integrins and resistance to apoptosis in human myeloma cell lines Blood 1999 93 1658 1667 10.1182/blood.V93.5.1658 10029595 PMC5550098 · DOI
  34. [34]Noborio-Hatano K. Kikuchi J. Takatoku M. Shimizu R. Wada T. Ueda M. Nobuyoshi M. Oh I. Sato K. Suzuki T. Bortezomib overcomes cell-adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma Oncogene 2009 28 231 242 10.1038/onc.2008.385 18850009 · DOI
  35. [35]Garcés J.J. Simicek M. Vicari M. Brozova L. Burgos L. Bezdekova R. Alignani D. Calasanz M.J. Growkova K. Goicoechea I. Transcriptional profiling of circulating tumor cells in multiple myeloma: A new model to understand disease dissemination Leukemia 2020 34 589 603 10.1038/s41375-019-0588-4 31595039 · DOI
  36. [36]Stessman H.A. Mansoor A. Zhan F. Janz S. Linden M.A. Baughn L.B. Van Ness B. Reduced CXCR4 expression is associated with extramedullary disease in a mouse model of myeloma and predicts poor survival in multiple myeloma patients treated with bortezomib Leukemia 2013 27 2075 2077 10.1038/leu.2013.148 23728080 PMC4053943 · DOI
  37. [37]Tarnowski M. Grymula K. Liu R. Tarnowska J. Drukala J. Ratajczak J. Mitchell R.A. Ratajczak M.Z. Kucia M. Macrophage migration inhibitory factor is secreted by rhabdomyosarcoma cells, modulates tumor metastasis by binding to CXCR4 and CXCR7 receptors and inhibits recruitment of cancer-associated fibroblasts Mol. Cancer Res. 2010 8 1328 1343 10.1158/1541-7786.MCR-10-0288 20861157 PMC2974061 · DOI · Paper page
  38. [38]Zheng Y. Wang Q. Li T. Qian J. Lu Y. Li Y. Bi E. Reu F. Qin Y. Drazba J. Role of Myeloma-Derived MIF in Myeloma Cell Adhesion to Bone Marrow and Chemotherapy Response J. Natl. Cancer Inst. 2016 108 10.1093/jnci/djw131 PMC5241902 27381622 · DOI
  39. [39]Vande Broek I. Leleu X. Schots R. Facon T. Vanderkerken K. Van Camp B. Van Riet I. Clinical significance of chemokine receptor (CCR1, CCR2 and CXCR4) expression in human myeloma cells: The association with disease activity and survival Haematologica 2006 91 200 206 16461304
  40. [40]Vandyke K. Zeissig M.N. Hewett D.R. Martin S.K. Mrozik K.M. Cheong C.M. Diamond P. To L.B. Gronthos S. Peet D.J. HIF-2alpha Promotes Dissemination of Plasma Cells in Multiple Myeloma by Regulating CXCL12/CXCR4 and CCR1 Cancer Res. 2017 77 5452 5463 10.1158/0008-5472.CAN-17-0115 28855206 · DOI
  41. [41]Hoggatt J. Kfoury Y. Scadden D.T. Hematopoietic Stem Cell Niche in Health and Disease Annu. Rev. Pathol. 2016 11 555 581 10.1146/annurev-pathol-012615-044414 27193455 · DOI
  42. [43]Wei Q. Frenette P.S. Niches for Hematopoietic Stem Cells and Their Progeny Immunity 2018 48 632 648 10.1016/j.immuni.2018.03.024 29669248 PMC6103525 · DOI
  43. [44]Kiel M.J. Yilmaz O.H. Iwashita T. Terhorst C. Morrison S.J. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells Cell 2005 121 1109 1121 10.1016/j.cell.2005.05.026 15989959 · DOI · Paper page
  44. [45]Pinho S. Frenette P.S. Haematopoietic stem cell activity and interactions with the niche Nat. Rev. Mol. Cell. Biol. 2019 20 303 320 10.1038/s41580-019-0103-9 30745579 PMC6483843 · DOI
  45. [46]Teixidó J. Hemler M.E. Greenberger J.S. Anklesaria P. Role of beta 1 and beta 2 integrins in the adhesion of human CD34hi stem cells to bone marrow stroma J. Clin. Investig. 1992 90 358 367 10.1172/JCI115870 1379610 PMC443110 · DOI
  46. [47]Simmons P.J. Masinovsky B. Longenecker B.M. Berenson R. Torok-Storb B. Gallatin W.M. Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates the binding of hematopoietic progenitor cells Blood 1992 80 388 395 10.1182/blood.V80.2.388.bloodjournal802388 1378318 · DOI
  47. [48]Vermeulen M. Le Pesteur F. Gagnerault M.C. Mary J.Y. Sainteny F. Lepault F. Role of adhesion molecules in the homing and mobilization of murine hematopoietic stem and progenitor cells Blood 1998 92 894 900 10.1182/blood.V92.3.894 9680357 · DOI
  48. [49]Lévesque J.P. Leavesley D.I. Niutta S. Vadas M. Simmons P.J. Cytokines increase human hemopoietic cell adhesiveness by activation of very late antigen (VLA)-4 and VLA-5 integrins J. Exp. Med. 1995 181 1805 1815 10.1084/jem.181.5.1805 7536795 PMC2192007 · DOI
  49. [50]Peled A. Kollet O. Ponomaryov T. Petit I. Franitza S. Grabovsky V. Slav M.M. Nagler A. Lider O. Alon R. The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 on immature human CD34(+) cells: Role in transendothelial/stromal migration and engraftment of NOD/SCID mice Blood 2000 95 3289 3296 10.1182/blood.V95.11.3289 10828007 · DOI
  50. [51]Schmits R. Filmus J. Gerwin N. Senaldi G. Kiefer F. Kundig T. Wakeham A. Shahinian A. Catzavelos C. Rak J. CD44 regulates hematopoietic progenitor distribution, granuloma formation, and tumorigenicity Blood 1997 90 2217 2233 10.1182/blood.V90.6.2217 9310473 · DOI
  51. [52]Frenette P.S. Subbarao S. Mazo I.B. von Andrian U.H. Wagner D.D. Endothelial selectins and vascular cell adhesion molecule-1 promote hematopoietic progenitor homing to bone marrow Proc. Natl. Acad. Sci. USA 1998 95 14423 14428 10.1073/pnas.95.24.14423 9826716 PMC24389 · DOI
  52. [53]Katayama Y. Hidalgo A. Furie B.C. Vestweber D. Furie B. Frenette P.S. PSGL-1 participates in E-selectin-mediated progenitor homing to bone marrow: Evidence for cooperation between E-selectin ligands and alpha4 integrin Blood 2003 102 2060 2067 10.1182/blood-2003-04-1212 12763924 · DOI
  53. [54]Singbrant S. Karlsson G. Ehinger M. Olsson K. Jaako P. Miharada K. Stadtfeld M. Graf T. Karlsson S. Canonical BMP signaling is dispensable for hematopoietic stem cell function in both adult and fetal liver hematopoiesis, but essential to preserve colon architecture Blood 2010 115 4689 4698 10.1182/blood-2009-05-220988 20371744 · DOI
  54. [55]Bernad A. Kopf M. Kulbacki R. Weich N. Koehler G. Gutierrez-Ramos J.C. Interleukin-6 is required in vivo for the regulation of stem cells and committed progenitors of the hematopoietic system Immunity 1994 1 725 731 10.1016/S1074-7613(94)80014-6 7895162 · DOI
  55. [56]Zhao M. Ross J.T. Itkin T. Perry J.M. Venkatraman A. Haug J.S. Hembree M.J. Deng C.X. Lapidot T. He X.C. FGF signaling facilitates postinjury recovery of mouse hematopoietic system Blood 2012 120 1831 1842 10.1182/blood-2011-11-393991 22802336 PMC3433089 · DOI
  56. [57]Karanu F.N. Murdoch B. Gallacher L. Wu D.M. Koremoto M. Sakano S. Bhatia M. The notch ligand jagged-1 represents a novel growth factor of human hematopoietic stem cells J. Exp. Med. 2000 192 1365 1372 10.1084/jem.192.9.1365 11067884 PMC2193352 · DOI
  57. [58]Stier S. Cheng T. Dombkowski D. Carlesso N. Scadden D.T. Notch1 activation increases hematopoietic stem cell self-renewal in vivo and favors lymphoid over myeloid lineage outcome Blood 2002 99 2369 2378 10.1182/blood.V99.7.2369 11895769 · DOI
  58. [59]Maillard I. Koch U. Dumortier A. Shestova O. Xu L. Sai H. Pross S.E. Aster J.C. Bhandoola A. Radtke F. Canonical notch signaling is dispensable for the maintenance of adult hematopoietic stem cells Cell Stem. Cell 2008 2 356 366 10.1016/j.stem.2008.02.011 18397755 PMC3717373 · DOI · Paper page
  59. [60]Yamazaki S. Ema H. Karlsson G. Yamaguchi T. Miyoshi H. Shioda S. Taketo M.M. Karlsson S. Iwama A. Nakauchi H. Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche Cell 2011 147 1146 1158 10.1016/j.cell.2011.09.053 22118468 · DOI
  60. [61]Sacchetti B. Funari A. Michienzi S. Di Cesare S. Piersanti S. Saggio I. Tagliafico E. Ferrari S. Robey P.G. Riminucci M. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment Cell 2007 131 324 336 10.1016/j.cell.2007.08.025 17956733 · DOI · Paper page
  61. [62]Chan C.K. Chen C.C. Luppen C.A. Kim J.B. DeBoer A.T. Wei K. Helms J.A. Kuo C.J. Kraft D.L. Weissman I.L. Endochondral ossification is required for haematopoietic stem-cell niche formation Nature 2009 457 490 494 10.1038/nature07547 19078959 PMC2648141 · DOI
  62. [63]Mendez-Ferrer S. Michurina T.V. Ferraro F. Mazloom A.R. Macarthur B.D. Lira S.A. Scadden D.T. Ma’ayan A. Enikolopov G.N. Frenette P.S. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche Nature 2010 466 829 834 10.1038/nature09262 20703299 PMC3146551 · DOI
  63. [64]Omatsu Y. Sugiyama T. Kohara H. Kondoh G. Fujii N. Kohno K. Nagasawa T. The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche Immunity 2010 33 387 399 10.1016/j.immuni.2010.08.017 20850355 · DOI
  64. [65]Chow A. Lucas D. Hidalgo A. Mendez-Ferrer S. Hashimoto D. Scheiermann C. Battista M. Leboeuf M. Prophete C. van Rooijen N. Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche J. Exp. Med. 2011 208 261 271 10.1084/jem.20101688 21282381 PMC3039855 · DOI
  65. [66]Winkler I.G. Sims N.A. Pettit A.R. Barbier V. Nowlan B. Helwani F. Poulton I.J. van Rooijen N. Alexander K.A. Raggatt L.J. Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs Blood 2010 116 4815 4828 10.1182/blood-2009-11-253534 20713966 · DOI · Paper page
  66. [67]Bruns I. Lucas D. Pinho S. Ahmed J. Lambert M.P. Kunisaki Y. Scheiermann C. Schiff L. Poncz M. Bergman A. Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion Nat. Med. 2014 20 1315 1320 10.1038/nm.3707 25326802 PMC4258871 · DOI
  67. [68]Zhao M. Perry J.M. Marshall H. Venkatraman A. Qian P. He X.C. Ahamed J. Li L. Megakaryocytes maintain homeostatic quiescence and promote post-injury regeneration of hematopoietic stem cells Nat. Med. 2014 20 1321 1326 10.1038/nm.3706 25326798 · DOI
  68. [69]Olson T.S. Caselli A. Otsuru S. Hofmann T.J. Williams R. Paolucci P. Dominici M. Horwitz E.M. Megakaryocytes promote murine osteoblastic HSC niche expansion and stem cell engraftment after radioablative conditioning Blood 2013 121 5238 5249 10.1182/blood-2012-10-463414 23667055 PMC3695366 · DOI
  69. [70]Staller P. Sulitkova J. Lisztwan J. Moch H. Oakeley E.J. Krek W. Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL Nature 2003 425 307 311 10.1038/nature01874 13679920 · DOI · Paper page
  70. [71]Danet G.H. Pan Y. Luongo J.L. Bonnet D.A. Simon M.C. Expansion of human SCID-repopulating cells under hypoxic conditions J. Clin. Investig. 2003 112 126 135 10.1172/JCI17669 12840067 PMC162287 · DOI
  71. [72]Ceradini D.J. Kulkarni A.R. Callaghan M.J. Tepper O.M. Bastidas N. Kleinman M.E. Capla J.M. Galiano R.D. Levine J.P. Gurtner G.C. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1 Nat. Med. 2004 10 858 864 10.1038/nm1075 15235597 · DOI · Paper page
  72. [73]Takubo K. Goda N. Yamada W. Iriuchishima H. Ikeda E. Kubota Y. Shima H. Johnson R.S. Hirao A. Suematsu M. Regulation of the HIF-1alpha level is essential for hematopoietic stem cells Cell Stem. Cell 2010 7 391 402 10.1016/j.stem.2010.06.020 20804974 · DOI · Paper page
  73. [74]Kunisaki Y. Bruns I. Scheiermann C. Ahmed J. Pinho S. Zhang D. Mizoguchi T. Wei Q. Lucas D. Ito K. Arteriolar niches maintain haematopoietic stem cell quiescence Nature 2013 502 637 643 10.1038/nature12612 24107994 PMC3821873 · DOI
  74. [75]Lucas D. Scheiermann C. Chow A. Kunisaki Y. Bruns I. Barrick C. Tessarollo L. Frenette P.S. Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration Nat. Med. 2013 19 695 703 10.1038/nm.3155 23644514 PMC3964478 · DOI
  75. [76]Mendez-Ferrer S. Lucas D. Battista M. Frenette P.S. Haematopoietic stem cell release is regulated by circadian oscillations Nature 2008 452 442 447 10.1038/nature06685 18256599 · DOI
  76. [77]Cyster J.G. Homing of antibody secreting cells Immunol Rev. 2003 194 48 60 10.1034/j.1600-065X.2003.00041.x 12846807 · DOI
  77. [78]Nutt S.L. Hodgkin P.D. Tarlinton D.M. Corcoran L.M. The generation of antibody-secreting plasma cells Nat. Rev. Immunol. 2015 15 160 171 10.1038/nri3795 25698678 · DOI
  78. [79]Tashiro K. Tada H. Heilker R. Shirozu M. Nakano T. Honjo T. Signal sequence trap: A cloning strategy for secreted proteins and type I membrane proteins Science 1993 261 600 603 10.1126/science.8342023 8342023 · DOI
  79. [80]Nagasawa T. Kikutani H. Kishimoto T. Molecular cloning and structure of a pre-B-cell growth-stimulating factor Proc. Natl. Acad. Sci. USA 1994 91 2305 2309 10.1073/pnas.91.6.2305 8134392 PMC43359 · DOI
  80. [81]Bleul C.C. Fuhlbrigge R.C. Casasnovas J.M. Aiuti A. Springer T.A. A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1) J. Exp. Med. 1996 184 1101 1109 10.1084/jem.184.3.1101 9064327 PMC2192798 · DOI · Paper page
  81. [82]Hauser A.E. Debes G.F. Arce S. Cassese G. Hamann A. Radbruch A. Manz R.A. Chemotactic responsiveness toward ligands for CXCR3 and CXCR4 is regulated on plasma blasts during the time course of a memory immune response J. Immunol. 2002 169 1277 1282 10.4049/jimmunol.169.3.1277 12133949 · DOI
  82. [83]Li Y.F. Xu S. Ou X. Lam K.P. Shp1 signalling is required to establish the long-lived bone marrow plasma cell pool Nat. Commun. 2014 5 4273 10.1038/ncomms5273 24978161 PMC4083441 · DOI
  83. [84]Minges Wols H.A. Underhill G.H. Kansas G.S. Witte P.L. The role of bone marrow-derived stromal cells in the maintenance of plasma cell longevity J. Immunol. 2002 169 4213 4221 10.4049/jimmunol.169.8.4213 12370351 · DOI
  84. [85]DiLillo D.J. Hamaguchi Y. Ueda Y. Yang K. Uchida J. Haas K.M. Kelsoe G. Tedder T.F. Maintenance of long-lived plasma cells and serological memory despite mature and memory B cell depletion during CD20 immunotherapy in mice J. Immunol. 2008 180 361 371 10.4049/jimmunol.180.1.361 18097037 · DOI
  85. [86]Zehentmeier S. Roth K. Cseresnyes Z. Sercan Ö. Horn K. Niesner R.A. Chang H.D. Radbruch A. Hauser A.E. Static and dynamic components synergize to form a stable survival niche for bone marrow plasma cells Eur. J. Immunol. 2014 44 2306 2317 10.1002/eji.201344313 24777940 · DOI
  86. [87]Pulido R. Elices M.J. Campanero M.R. Osborn L. Schiffer S. García-Pardo A. Lobb R. Hemler M.E. Sánchez-Madrid F. Functional evidence for three distinct and independently inhibitable adhesion activities mediated by the human integrin VLA-4. Correlation with distinct alpha 4 epitopes J. Biol. Chem. 1991 266 10241 10245 10.1016/S0021-9258(18)99215-X 1709929 · DOI
  87. [88]Nguyen D.C. Garimalla S. Xiao H. Kyu S. Albizua I. Galipeau J. Chiang K.Y. Waller E.K. Wu R. Gibson G. Factors of the bone marrow microniche that support human plasma cell survival and immunoglobulin secretion Nat. Commun. 2018 9 3698 10.1038/s41467-018-05853-7 30209264 PMC6135805 · DOI
  88. [89]Baryawno N. Przybylski D. Kowalczyk M.S. Kfoury Y. Severe N. Gustafsson K. Kokkaliaris K.D. Mercier F. Tabaka M. Hofree M. A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia Cell 2019 177 1915 1932.e16 10.1016/j.cell.2019.04.040 31130381 PMC6570562 · DOI
  89. [90]Kawano M.M. Mihara K. Huang N. Tsujimoto T. Kuramoto A. Differentiation of early plasma cells on bone marrow stromal cells requires interleukin-6 for escaping from apoptosis Blood 1995 85 487 494 10.1182/blood.V85.2.487.487 7812003 · DOI
  90. [91]Chu V.T. Fröhlich A. Steinhauser G. Scheel T. Roch T. Fillatreau S. Lee J.J. Löhning M. Berek C. Eosinophils are required for the maintenance of plasma cells in the bone marrow Nat. Immunol. 2011 12 151 159 10.1038/ni.1981 21217761 · DOI
  91. [92]Haberland K. Ackermann J.A. Ipseiz N. Culemann S. Pracht K. Englbrecht M. Jäck H.M. Schett G. Schuh W. Krönke G. Eosinophils are not essential for maintenance of murine plasma cells in the bone marrow Eur. J. Immunol. 2018 48 822 828 10.1002/eji.201747227 29442374 · DOI
  92. [93]Bortnick A. Chernova I. Spencer S.P. Allman D. No strict requirement for eosinophils for bone marrow plasma cell survival Eur. J. Immunol. 2018 48 815 821 10.1002/eji.201747229 29442367 · DOI
  93. [94]Winter O. Moser K. Mohr E. Zotos D. Kaminski H. Szyska M. Roth K. Wong D.M. Dame C. Tarlinton D.M. Megakaryocytes constitute a functional component of a plasma cell niche in the bone marrow Blood 2010 116 1867 1875 10.1182/blood-2009-12-259457 20538807 · DOI
  94. [95]Benson M.J. Dillon S.R. Castigli E. Geha R.S. Xu S. Lam K.P. Noelle R.J. Cutting edge: The dependence of plasma cells and independence of memory B cells on BAFF and APRIL J. Immunol. 2008 180 3655 3659 10.4049/jimmunol.180.6.3655 18322170 · DOI
  95. [96]Walkley C.R. Olsen G.H. Dworkin S. Fabb S.A. Swann J. McArthur G.A. Westmoreland S.V. Chambon P. Scadden D.T. Purton L.E. A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency Cell 2007 129 1097 1110 10.1016/j.cell.2007.05.014 17574023 PMC1974882 · DOI
  96. [97]Dong L. Yu W.M. Zheng H. Loh M.L. Bunting S.T. Pauly M. Huang G. Zhou M. Broxmeyer H.E. Scadden D.T. Leukaemogenic effects of Ptpn11 activating mutations in the stem cell microenvironment Nature 2016 539 304 308 10.1038/nature20131 27783593 PMC5317374 · DOI
  97. [98]Wortzel I. Dror S. Kenific C.M. Lyden D. Exosome-Mediated Metastasis: Communication from a Distance Dev. Cell 2019 49 347 360 10.1016/j.devcel.2019.04.011 31063754 · DOI
  98. [99]Théry C. Zitvogel L. Amigorena S. Exosomes: Composition, biogenesis and function Nat. Rev. Immunol. 2002 2 569 579 10.1038/nri855 12154376 · DOI
  99. [100]Mathieu M. Martin-Jaular L. Lavieu G. Théry C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication Nat. Cell Biol. 2019 21 9 17 10.1038/s41556-018-0250-9 30602770 · DOI
  100. [101]Roccaro A.M. Sacco A. Maiso P. Azab A.K. Tai Y.T. Reagan M. Azab F. Flores L.M. Campigotto F. Weller E. BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression J. Clin. Investig. 2013 123 1542 1555 10.1172/JCI66517 23454749 PMC3613927 · DOI
  101. [102]Wang J. Hendrix A. Hernot S. Lemaire M. De Bruyne E. Van Valckenborgh E. Lahoutte T. De Wever O. Vanderkerken K. Menu E. Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells Blood 2014 124 555 566 10.1182/blood-2014-03-562439 24928860 · DOI
  102. [103]Raimondi L. De Luca A. Amodio N. Manno M. Raccosta S. Taverna S. Bellavia D. Naselli F. Fontana S. Schillaci O. Involvement of multiple myeloma cell-derived exosomes in osteoclast differentiation Oncotarget 2015 6 13772 13789 10.18632/oncotarget.3830 25944696 PMC4537049 · DOI
  103. [105]Colmone A. Amorim M. Pontier A.L. Wang S. Jablonski E. Sipkins D.A. Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells Science 2008 322 1861 1865 10.1126/science.1164390 19095944 · DOI
  104. [106]Boyd A.L. Campbell C.J. Hopkins C.I. Fiebig-Comyn A. Russell J. Ulemek J. Foley R. Leber B. Xenocostas A. Collins T.J. Niche displacement of human leukemic stem cells uniquely allows their competitive replacement with healthy HSPCs J. Exp. Med. 2014 211 1925 1935 10.1084/jem.20140131 25180064 PMC4172227 · DOI
  105. [107]Akinduro O. Weber T.S. Ang H. Haltalli M.L.R. Ruivo N. Duarte D. Rashidi N.M. Hawkins E.D. Duffy K.R. Lo Celso C. Proliferation dynamics of acute myeloid leukaemia and haematopoietic progenitors competing for bone marrow space Nat. Commun. 2018 9 519 10.1038/s41467-017-02376-5 29410432 PMC5802720 · DOI
  106. [108]Kuehl W.M. Bergsagel P.L. Molecular pathogenesis of multiple myeloma and its premalignant precursor J. Clin. Investig. 2012 122 3456 3463 10.1172/JCI61188 23023717 PMC3461901 · DOI
  107. [109]Giuliani N. Rizzoli V. Roodman G.D. Multiple myeloma bone disease: Pathophysiology of osteoblast inhibition Blood 2006 108 3992 3996 10.1182/blood-2006-05-026112 16917004 · DOI · Paper page
  108. [110]Raje N. Roodman G.D. Advances in the biology and treatment of bone disease in multiple myeloma Clin. Cancer Res. 2011 17 1278 1286 10.1158/1078-0432.CCR-10-1804 21411443 · DOI
  109. [111]Ghajar C.M. Metastasis prevention by targeting the dormant niche Nat. Rev. Cancer 2015 15 238 247 10.1038/nrc3910 25801619 PMC4842412 · DOI
  110. [112]Chen Z. Orlowski R.Z. Wang M. Kwak L. McCarty N. Osteoblastic niche supports the growth of quiescent multiple myeloma cells Blood 2014 123 2204 2208 10.1182/blood-2013-07-517136 24425802 PMC3975258 · DOI
  111. [113]Khoo W.H. Ledergor G. Weiner A. Roden D.L. Terry R.L. McDonald M.M. Chai R.C. De Veirman K. Owen K.L. Opperman K.S. A niche-dependent myeloid transcriptome signature defines dormant myeloma cells Blood 2019 134 30 43 10.1182/blood.2018880930 31023703 · DOI
  112. [114]Lawson M.A. McDonald M.M. Kovacic N. Hua Khoo W. Terry R.L. Down J. Kaplan W. Paton-Hough J. Fellows C. Pettitt J.A. Osteoclasts control reactivation of dormant myeloma cells by remodelling the endosteal niche Nat. Commun. 2015 6 8983 10.1038/ncomms9983 26632274 PMC4686867 · DOI
  113. [115]Roodman G.D. Osteoblast function in myeloma Bone 2011 48 135 140 10.1016/j.bone.2010.06.016 20601285 · DOI
  114. [116]Tian E. Zhan F. Walker R. Rasmussen E. Ma Y. Barlogie B. Shaughnessy J.D. Jr. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma N. Engl. J. Med. 2003 349 2483 2494 10.1056/NEJMoa030847 14695408 · DOI
  115. [117]Heath D.J. Chantry A.D. Buckle C.H. Coulton L. Shaughnessy J.D. Jr. Evans H.R. Snowden J.A. Stover D.R. Vanderkerken K. Croucher P.I. Inhibiting Dickkopf-1 (Dkk1) removes suppression of bone formation and prevents the development of osteolytic bone disease in multiple myeloma J. Bone Miner. Res. 2009 24 425 436 10.1359/jbmr.081104 19016584 · DOI
  116. [119]Bolzoni M. Donofrio G. Storti P. Guasco D. Toscani D. Lazzaretti M. Bonomini S. Agnelli L. Capocefalo A. Dalla Palma B. Myeloma cells inhibit non-canonical wnt co-receptor ror2 expression in human bone marrow osteoprogenitor cells: Effect of wnt5a/ror2 pathway activation on the osteogenic differentiation impairment induced by myeloma cells Leukemia 2013 27 451 463 10.1038/leu.2012.190 22781592 · DOI
  117. [120]Frenquelli M. Caridi N. Antonini E. Storti F. Viganò V. Gaviraghi M. Occhionorelli M. Bianchessi S. Bongiovanni L. Spinelli A. The WNT receptor ROR2 drives the interaction of multiple myeloma cells with the microenvironment through AKT activation Leukemia 2020 34 257 270 10.1038/s41375-019-0486-9 31148590 PMC7617051 · DOI
  118. [121]Mirandola L. Apicella L. Colombo M. Yu Y. Berta D.G. Platonova N. Lazzari E. Lancellotti M. Bulfamante G. Cobos E. Anti-Notch treatment prevents multiple myeloma cells localization to the bone marrow via the chemokine system CXCR4/SDF-1 Leukemia 2013 27 1558 1566 10.1038/leu.2013.27 23354012 · DOI
  119. [122]Jundt F. Pröbsting K.S. Anagnostopoulos I. Muehlinghaus G. Chatterjee M. Mathas S. Bargou R.C. Manz R. Stein H. Dörken B. Jagged1-induced Notch signaling drives proliferation of multiple myeloma cells Blood 2004 103 3511 3515 10.1182/blood-2003-07-2254 14726396 · DOI
  120. [123]Houde C. Li Y. Song L. Barton K. Zhang Q. Godwin J. Nand S. Toor A. Alkan S. Smadja N.V. Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines Blood 2004 104 3697 3704 10.1182/blood-2003-12-4114 15292061 · DOI
  121. [124]Giuliani N. Colla S. Morandi F. Lazzaretti M. Sala R. Bonomini S. Grano M. Colucci S. Svaldi M. Rizzoli V. Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation Blood 2005 106 2472 2483 10.1182/blood-2004-12-4986 15933061 · DOI
  122. [127]Kawano Y. Moschetta M. Manier S. Glavey S. Görgün G.T. Roccaro A.M. Anderson K.C. Ghobrial I.M. Targeting the bone marrow microenvironment in multiple myeloma Immunol. Rev. 2015 263 160 172 10.1111/imr.12233 25510276 · DOI
  123. [128]Gupta D. Treon S.P. Shima Y. Hideshima T. Podar K. Tai Y.T. Lin B. Lentzsch S. Davies F.E. Chauhan D. Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: Therapeutic applications Leukemia 2001 15 1950 1961 10.1038/sj.leu.2402295 11753617 · DOI
  124. [129]Tanno T. Lim Y. Wang Q. Chesi M. Bergsagel P.L. Matthews G. Johnstone R.W. Ghosh N. Borrello I. Huff C.A. Growth differentiating factor 15 enhances the tumor-initiating and self-renewal potential of multiple myeloma cells Blood 2014 123 725 733 10.1182/blood-2013-08-524025 24345755 PMC3907757 · DOI
  125. [130]Nakamura K. Smyth M.J. Martinet L. Cancer immunoediting and immune dysregulation in multiple myeloma Blood 2020 10.1182/blood.2020006540 32645135 · DOI
  126. [131]Hoyos V. Borrello I. The immunotherapy era of myeloma: Monoclonal antibodies, vaccines, and adoptive T-cell therapies Blood 2016 128 1679 1687 10.1182/blood-2016-05-636357 27506540 · DOI
  127. [132]Cohen A.D. Raje N. Fowler J.A. Mezzi K. Scott E.C. Dhodapkar M.V. How to Train Your T Cells: Overcoming Immune Dysfunction in Multiple Myeloma Clin. Cancer Res. 2020 26 1541 1554 10.1158/1078-0432.CCR-19-2111 31672768 PMC8176627 · DOI
  128. [133]Xu S. De Veirman K. De Becker A. Vanderkerken K. Van Riet I. Mesenchymal stem cells in multiple myeloma: A therapeutical tool or target? Leukemia 2018 32 1500 1514 10.1038/s41375-018-0061-9 29535427 PMC6035148 · DOI
  129. [134]Lomas O.C. Tahri S. Ghobrial I.M. The microenvironment in myeloma Curr. Opin. Oncol. 2020 32 170 175 10.1097/CCO.0000000000000615 31895122 · DOI
  130. [135]Zheng Y. Cai Z. Wang S. Zhang X. Qian J. Hong S. Li H. Wang M. Yang J. Yi Q. Macrophages are an abundant component of myeloma microenvironment and protect myeloma cells from chemotherapy drug-induced apoptosis Blood 2009 114 3625 3628 10.1182/blood-2009-05-220285 19710503 PMC2766678 · DOI
  131. [136]Lorenzo-Sanz L. Muñoz P. Tumor-Infiltrating Immunosuppressive Cells in Cancer-Cell Plasticity, Tumor Progression and Therapy Response Cancer Microenviron 2019 12 119 132 10.1007/s12307-019-00232-2 31583529 PMC6937363 · DOI
  132. [137]Petty A.J. Yang Y. Tumor-Associated Macrophages in Hematologic Malignancies: New Insights and Targeted Therapies Cells 2019 8 1526 10.3390/cells8121526 PMC6952752 31783588 · DOI
  133. [138]Beider K. Bitner H. Leiba M. Gutwein O. Koren-Michowitz M. Ostrovsky O. Abraham M. Wald H. Galun E. Peled A. Multiple myeloma cells recruit tumor-supportive macrophages through the CXCR4/CXCL12 axis and promote their polarization toward the M2 phenotype Oncotarget 2014 5 11283 11296 10.18632/oncotarget.2207 25526031 PMC4294328 · DOI
  134. [139]Chen H. Li M. Sanchez E. Soof C.M. Bujarski S. Ng N. Cao J. Hekmati T. Zahab B. Nosrati J.D. JAK1/2 pathway inhibition suppresses M2 polarization and overcomes resistance of myeloma to lenalidomide by reducing TRIB1, MUC1, CD44, CXCL12, and CXCR4 expression Br. J. Haematol. 2020 188 283 294 10.1111/bjh.16158 31423579 · DOI
  135. [140]Li Y. Zheng Y. Li T. Wang Q. Qian J. Lu Y. Zhang M. Bi E. Yang M. Reu F. Chemokines CCL2, 3, 14 stimulate macrophage bone marrow homing, proliferation, and polarization in multiple myeloma Oncotarget 2015 6 24218 24229 10.18632/oncotarget.4523 26155942 PMC4695181 · DOI
  136. [141]De Beule N. De Veirman K. Maes K. De Bruyne E. Menu E. Breckpot K. De Raeve H. Van Rampelbergh R. Van Ginderachter J.A. Schots R. Tumour-associated macrophage-mediated survival of myeloma cells through STAT3 activation J. Pathol. 2017 241 534 546 10.1002/path.4860 27976373 · DOI
  137. [142]Wang Q. Lu Y. Li R. Jiang Y. Zheng Y. Qian J. Bi E. Zheng C. Hou J. Wang S. Therapeutic effects of CSF1R-blocking antibodies in multiple myeloma Leukemia 2018 32 176 183 10.1038/leu.2017.193 28626216 PMC5927777 · DOI
  138. [143]Chen X. Chen J. Zhang W. Sun R. Liu T. Zheng Y. Wu Y. Prognostic value of diametrically polarized tumor-associated macrophages in multiple myeloma Oncotarget 2017 8 112685 112696 10.18632/oncotarget.22340 29348856 PMC5762541 · DOI
  139. [144]Wang H. Hu W.M. Xia Z.J. Liang Y. Lu Y. Lin S.X. Tang H. High numbers of CD163+ tumor-associated macrophages correlate with poor prognosis in multiple myeloma patients receiving bortezomib-based regimens J. Cancer 2019 10 3239 3245 10.7150/jca.30102 31289595 PMC6603386 · DOI
  140. [145]Panchabhai S. Kelemen K. Ahmann G. Sebastian S. Mantei J. Fonseca R. Tumor-associated macrophages and extracellular matrix metalloproteinase inducer in prognosis of multiple myeloma Leukemia 2016 30 951 954 10.1038/leu.2015.191 26202926 · DOI
  141. [146]Andersen M.N. Andersen N.F. Rødgaard-Hansen S. Hokland M. Abildgaard N. Møller H.J. The novel biomarker of alternative macrophage activation, soluble mannose receptor (sMR/sCD206): Implications in multiple myeloma Leuk. Res. 2015 39 971 975 10.1016/j.leukres.2015.06.003 26169445 · DOI
  142. [147]Wang Q. Zhao D. Xian M. Wang Z. Bi E. Su P. Qian J. Ma X. Yang M. Liu L. MIF as a biomarker and therapeutic target for overcoming resistance to proteasome inhibitors in human myeloma Blood 2020 10.1182/blood.2020005795 PMC7714094 32582913 · DOI
  143. [148]Xu R. Li Y. Yan H. Zhang E. Huang X. Chen Q. Chen J. Qu J. Liu Y. He J. CCL2 promotes macrophages-associated chemoresistance via MCPIP1 dual catalytic activities in multiple myeloma Cell Death Dis. 2019 10 781 10.1038/s41419-019-2012-4 31611552 PMC6791869 · DOI
  144. [149]Kim J. Denu R.A. Dollar B.A. Escalante L.E. Kuether J.P. Callander N.S. Asimakopoulos F. Hematti P. Macrophages and mesenchymal stromal cells support survival and proliferation of multiple myeloma cells Br. J. Haematol. 2012 158 336 346 10.1111/j.1365-2141.2012.09154.x 22583117 PMC3395762 · DOI
  145. [150]Zheng Y. Yang J. Qian J. Qiu P. Hanabuchi S. Lu Y. Wang Z. Liu Z. Li H. He J. PSGL-1/selectin and ICAM-1/CD18 interactions are involved in macrophage-induced drug resistance in myeloma Leukemia 2013 27 702 710 10.1038/leu.2012.272 22996336 PMC3652581 · DOI
  146. [151]Beyar-Katz O. Magidey K. Ben-Tsedek N. Alishekevitz D. Timaner M. Miller V. Lindzen M. Yarden Y. Avivi I. Shaked Y. Bortezomib-induced pro-inflammatory macrophages as a potential factor limiting anti-tumour efficacy J. Pathol. 2016 239 262 273 10.1002/path.4723 27037906 · DOI
  147. [152]Minnie S.A. Kuns R.D. Gartlan K.H. Zhang P. Wilkinson A.N. Samson L. Guillerey C. Engwerda C. MacDonald K.P.A. Smyth M.J. Myeloma escape after stem cell transplantation is a consequence of T-cell exhaustion and is prevented by TIGIT blockade Blood 2018 132 1675 1688 10.1182/blood-2018-01-825240 30154111 · DOI
  148. [153]Opperman K.S. Vandyke K. Clark K.C. Coulter E.A. Hewett D.R. Mrozik K.M. Schwarz N. Evdokiou A. Croucher P.I. Psaltis P.J. Clodronate-Liposome Mediated Macrophage Depletion Abrogates Multiple Myeloma Tumor Establishment In Vivo Neoplasia 2019 21 777 787 10.1016/j.neo.2019.05.006 31247457 PMC6593350 · DOI
  149. [154]Scavelli C. Nico B. Cirulli T. Ria R. Di Pietro G. Mangieri D. Bacigalupo A. Mangialardi G. Coluccia A.M. Caravita T. Vasculogenic mimicry by bone marrow macrophages in patients with multiple myeloma Oncogene 2008 27 663 674 10.1038/sj.onc.1210691 17667938 · DOI
  150. [155]Alexandrakis M.G. Goulidaki N. Pappa C.A. Boula A. Psarakis F. Neonakis I. Tsirakis G. Interleukin-10 Induces Both Plasma Cell Proliferation and Angiogenesis in Multiple Myeloma Pathol. Oncol. Res. 2015 21 929 934 10.1007/s12253-015-9921-z 25743259 · DOI
  151. [156]Berardi S. Ria R. Reale A. De Luisi A. Catacchio I. Moschetta M. Vacca A. Multiple myeloma macrophages: Pivotal players in the tumor microenvironment J. Oncol. 2013 2013 183602 10.1155/2013/183602 23431298 PMC3570938 · DOI
  152. [157]Bogen B. Fauskanger M. Haabeth O.A. Tveita A. CD4(+) T cells indirectly kill tumor cells via induction of cytotoxic macrophages in mouse models Cancer Immunol. Immunother 2019 68 1865 1873 10.1007/s00262-019-02374-0 31448380 PMC11028095 · DOI
  153. [158]Haabeth O.A.W. Hennig K. Fauskanger M. Løset G. Bogen B. Tveita A. CD4+ T-cell killing of multiple myeloma cells is mediated by resident bone marrow macrophages Blood Adv. 2020 4 2595 2605 10.1182/bloodadvances.2020001434 32544236 PMC7322971 · DOI
  154. [159]Fauskanger M. Haabeth O.A.W. Skjeldal F.M. Bogen B. Tveita A.A. Tumor Killing by CD4+ T Cells Is Mediated via Induction of Inducible Nitric Oxide Synthase-Dependent Macrophage Cytotoxicity Front Immunol. 2018 9 1684 10.3389/fimmu.2018.01684 30083157 PMC6064871 · DOI
  155. [160]Haabeth O.A. Lorvik K.B. Hammarström C. Donaldson I.M. Haraldsen G. Bogen B. Corthay A. Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer Nat. Commun. 2011 2 240 10.1038/ncomms1239 21407206 PMC3072106 · DOI
  156. [161]Tveita A.A. Schjesvold F. Haabeth O.A. Fauskanger M. Bogen B. Tumors Escape CD4+ T-cell-Mediated Immunosurveillance by Impairing the Ability of Infiltrating Macrophages to Indirectly Present Tumor Antigens Cancer Res. 2015 75 3268 3278 10.1158/0008-5472.CAN-14-3640 26038231 · DOI
  157. [162]Tveita A.A. Schjesvold F.H. Sundnes O. Haabeth O.A. Haraldsen G. Bogen B. Indirect CD4+ T-cell-mediated elimination of MHC II(NEG) tumor cells is spatially restricted and fails to prevent escape of antigen-negative cells Eur. J. Immunol. 2014 44 2625 2637 10.1002/eji.201444659 24846412 · DOI
  158. [163]Gutiérrez-González A. Martínez-Moreno M. Samaniego R. Arellano-Sánchez N. Salinas-Muñoz L. Relloso M. Valeri A. Martínez-López J. Corbí Á.L. Hidalgo A. Evaluation of the potential therapeutic benefits of macrophage reprogramming in multiple myeloma Blood 2016 128 2241 2252 10.1182/blood-2016-01-695395 27625360 · DOI
  159. [164]Lee S.E. Lim J.Y. Ryu D.B. Kim T.W. Yoon J.H. Cho B.S. Eom K.S. Kim Y.J. Kim H.J. Lee S. Circulating immune cell phenotype can predict the outcome of lenalidomide plus low-dose dexamethasone treatment in patients with refractory/relapsed multiple myeloma Cancer Immunol. Immunother 2016 65 983 994 10.1007/s00262-016-1861-2 27342591 PMC11029332 · DOI
  160. [165]Giallongo C. Tibullo D. Parrinello N.L. La Cava P. Di Rosa M. Bramanti V. Di Raimondo C. Conticello C. Chiarenza A. Palumbo G.A. Granulocyte-like myeloid derived suppressor cells (G-MDSC) are increased in multiple myeloma and are driven by dysfunctional mesenchymal stem cells (MSC) Oncotarget 2016 7 85764 85775 10.18632/oncotarget.7969 26967390 PMC5349872 · DOI
  161. [166]Favaloro J. Liyadipitiya T. Brown R. Yang S. Suen H. Woodland N. Nassif N. Hart D. Fromm P. Weatherburn C. Myeloid derived suppressor cells are numerically, functionally and phenotypically different in patients with multiple myeloma Leuk. Lymphoma 2014 55 2893 2900 10.3109/10428194.2014.904511 24625328 · DOI
  162. [167]Tai Y.T. Lin L. Xing L. Cho S.F. Yu T. Acharya C. Wen K. Hsieh P.A. Dulos J. van Elsas A. APRIL signaling via TACI mediates immunosuppression by T regulatory cells in multiple myeloma: Therapeutic implications Leukemia 2019 33 426 438 10.1038/s41375-018-0242-6 30135465 PMC6367000 · DOI
  163. [168]Romano A. Parrinello N.L. La Cava P. Tibullo D. Giallongo C. Camiolo G. Puglisi F. Parisi M. Pirosa M.C. Martino E. PMN-MDSC and arginase are increased in myeloma and may contribute to resistance to therapy Expert Rev. Mol. Diagn. 2018 18 675 683 10.1080/14737159.2018.1470929 29707981 · DOI
  164. [169]Wang Z. Zhang L. Wang H. Xiong S. Li Y. Tao Q. Xiao W. Qin H. Wang Y. Zhai Z. Tumor-induced CD14+HLA-DR (-/low) myeloid-derived suppressor cells correlate with tumor progression and outcome of therapy in multiple myeloma patients Cancer Immunol. Immunother 2015 64 389 399 10.1007/s00262-014-1646-4 25548095 PMC11028624 · DOI
  165. [170]Kuwahara-Ota S. Shimura Y. Steinebach C. Isa R. Yamaguchi J. Nishiyama D. Fujibayashi Y. Takimoto-Shimomura T. Mizuno Y. Matsumura-Kimoto Y. Lenalidomide and pomalidomide potently interfere with induction of myeloid-derived suppressor cells in multiple myeloma Br. J. Haematol. 2020 10.1111/bjh.16881 32558939 · DOI
  166. [171]Gorgun G. Samur M.K. Cowens K.B. Paula S. Bianchi G. Anderson J.E. White R.E. Singh A. Ohguchi H. Suzuki R. Lenalidomide Enhances Immune Checkpoint Blockade-Induced Immune Response in Multiple Myeloma Clin. Cancer Res. 2015 21 4607 4618 10.1158/1078-0432.CCR-15-0200 25979485 PMC4609232 · DOI · Paper page
  167. [172]De Veirman K. Van Ginderachter J.A. Lub S. De Beule N. Thielemans K. Bautmans I. Oyajobi B.O. De Bruyne E. Menu E. Lemaire M. Multiple myeloma induces Mcl-1 expression and survival of myeloid-derived suppressor cells Oncotarget 2015 6 10532 10547 10.18632/oncotarget.3300 25871384 PMC4496373 · DOI
  168. [173]Zhou J. Lin H. Hu L. Li G. Zhang X. Decitabine shows potent anti-myeloma activity by depleting monocytic myeloid-derived suppressor cells in the myeloma microenvironment J. Cancer Res. Clin. Oncol. 2019 145 329 336 10.1007/s00432-018-2790-6 30426212 PMC11810327 · DOI
  169. [174]Wang J. De Veirman K. Faict S. Frassanito M.A. Ribatti D. Vacca A. Menu E. Multiple myeloma exosomes establish a favourable bone marrow microenvironment with enhanced angiogenesis and immunosuppression J. Pathol. 2016 239 162 173 10.1002/path.4712 26956697 · DOI
  170. [175]Wang J. De Veirman K. De Beule N. Maes K. De Bruyne E. Van Valckenborgh E. Vanderkerken K. Menu E. The bone marrow microenvironment enhances multiple myeloma progression by exosome-mediated activation of myeloid-derived suppressor cells Oncotarget 2015 6 43992 44004 10.18632/oncotarget.6083 26556857 PMC4791281 · DOI
  171. [176]Leone P. Berardi S. Frassanito M.A. Ria R. De Re V. Cicco S. Battaglia S. Ditonno P. Dammacco F. Vacca A. Dendritic cells accumulate in the bone marrow of myeloma patients where they protect tumor plasma cells from CD8+ T-cell killing Blood 2015 126 1443 1451 10.1182/blood-2015-01-623975 26185130 PMC4592278 · DOI
  172. [177]Ray A. Das D.S. Song Y. Macri V. Richardson P. Brooks C.L. Chauhan D. Anderson K.C. A novel agent SL-401 induces anti-myeloma activity by targeting plasmacytoid dendritic cells, osteoclastogenesis and cancer stem-like cells Leukemia 2017 31 2652 2660 10.1038/leu.2017.135 28479592 PMC5737925 · DOI
  173. [178]Lamarthee B. de Vassoigne F. Malard F. Stocker N. Boussen I. Mediavilla C. Tang R. Fava F. Garderet L. Marjanovic Z. Quantitative and functional alterations of 6-sulfo LacNac dendritic cells in multiple myeloma Oncoimmunology 2018 7 e1444411 10.1080/2162402X.2018.1444411 29900053 PMC5993501 · DOI
  174. [179]Shinde P. Fernandes S. Melinkeri S. Kale V. Limaye L. Compromised functionality of monocyte-derived dendritic cells in multiple myeloma patients may limit their use in cancer immunotherapy Sci. Rep. 2018 8 5705 10.1038/s41598-018-23943-w 29632307 PMC5890285 · DOI
  175. [180]Romano A. Parrinello N.L. Simeon V. Puglisi F. La Cava P. Bellofiore C. Giallongo C. Camiolo G. D’Auria F. Grieco V. High-density neutrophils in MGUS and multiple myeloma are dysfunctional and immune-suppressive due to increased STAT3 downstream signaling Sci. Rep. 2020 10 1983 10.1038/s41598-020-58859-x 32029833 PMC7005058 · DOI
  176. [181]Puglisi F. Parrinello N.L. Giallongo C. Cambria D. Camiolo G. Bellofiore C. Conticello C. Del Fabro V. Leotta V. Markovic U. Plasticity of High-Density Neutrophils in Multiple Myeloma is Associated with Increased Autophagy Via STAT3 Int. J. Mol. Sci. 2019 20 3548 10.3390/ijms20143548 32565533 PMC6678548 · DOI
  177. [182]Perez C. Botta C. Zabaleta A. Puig N. Cedena M.T. Goicoechea I. Alameda D. San Jose-Eneriz E. Merino J. Rodriguez-Otero P. Immunogenomic identification and characterization of granulocytic myeloid-derived suppressor cells in multiple myeloma Blood 2020 136 199 209 10.1182/blood.2019004537 32325491 · DOI
  178. [183]Wong T.W. Kita H. Hanson C.A. Walters D.K. Arendt B.K. Jelinek D.F. Induction of malignant plasma cell proliferation by eosinophils PLoS ONE 2013 8 e70554 10.1371/journal.pone.0070554 23894671 PMC3718740 · DOI
  179. [184]Glatman Zaretsky A. Konradt C. Dépis F. Wing J.B. Goenka R. Atria D.G. Silver J.S. Cho S. Wolf A.I. Quinn W.J. T Regulatory Cells Support Plasma Cell Populations in the Bone Marrow Cell Rep. 2017 18 1906 1916 10.1016/j.celrep.2017.01.067 28228257 PMC5361408 · DOI
  180. [185]Vyzoukaki R. Tsirakis G. Pappa C.A. Devetzoglou M. Tzardi M. Alexandrakis M.G. The Impact of Mast Cell Density on the Progression of Bone Disease in Multiple Myeloma Patients Int. Arch Allergy Immunol. 2015 168 263 268 10.1159/000443275 26894886 · DOI
  181. [186]Takagi S. Tsukamoto S. Park J. Johnson K.E. Kawano Y. Moschetta M. Liu C.J. Mishima Y. Kokubun K. Manier S. Platelets Enhance Multiple Myeloma Progression via IL-1beta Upregulation Clin. Cancer Res. 2018 24 2430 2439 10.1158/1078-0432.CCR-17-2003 29440174 · DOI
  182. [187]Prabhala R.H. Pelluru D. Fulciniti M. Prabhala H.K. Nanjappa P. Song W. Pai C. Amin S. Tai Y.T. Richardson P.G. Elevated IL-17 produced by TH17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma Blood 2010 115 5385 5392 10.1182/blood-2009-10-246660 20395418 PMC2902136 · DOI
  183. [188]Bryant C. Suen H. Brown R. Yang S. Favaloro J. Aklilu E. Gibson J. Ho P.J. Iland H. Fromm P. Long-term survival in multiple myeloma is associated with a distinct immunological profile, which includes proliferative cytotoxic T-cell clones and a favourable Treg/Th17 balance Blood Cancer J. 2013 3 e148 10.1038/bcj.2013.34 24036947 PMC3789202 · DOI
  184. [189]Lad D. Huang Q. Hoeppli R. Garcia R. Xu L. Levings M. Song K. Broady R. Evaluating the role of Tregs in the progression of multiple myeloma Leuk. Lymphoma 2019 60 2134 2142 10.1080/10428194.2019.1579324 30773086 · DOI
  185. [190]Alrasheed N. Lee L. Ghorani E. Henry J.Y. Conde L. Chin M. Galas-Filipowicz D. Furness A.J.S. Chavda S.J. Richards H. Marrow-Infiltrating Regulatory T Cells Correlate with the Presence of Dysfunctional CD4+PD-1+ Cells and Inferior Survival in Patients with Newly Diagnosed Multiple Myeloma Clin. Cancer Res. 2020 26 3443 3454 10.1158/1078-0432.CCR-19-1714 32220887 · DOI
  186. [191]Giannopoulos K. Kaminska W. Hus I. Dmoszynska A. The frequency of T regulatory cells modulates the survival of multiple myeloma patients: Detailed characterisation of immune status in multiple myeloma Br. J. Cancer 2012 106 546 552 10.1038/bjc.2011.575 22223085 PMC3273338 · DOI
  187. [192]Wang J.N. Cao X.X. Zhao A.L. Cai H. Wang X. Li J. Increased activated regulatory T cell subsets and aging Treg-like cells in multiple myeloma and monoclonal gammopathy of undetermined significance: A case control study Cancer Cell Int. 2018 18 187 10.1186/s12935-018-0687-8 30479566 PMC6245875 · DOI
  188. [193]Kawano Y. Zavidij O. Park J. Moschetta M. Kokubun K. Mouhieddine T.H. Manier S. Mishima Y. Murakami N. Bustoros M. Blocking IFNAR1 inhibits multiple myeloma-driven Treg expansion and immunosuppression J. Clin. Investig. 2018 128 2487 2499 10.1172/JCI88169 29558366 PMC5983341 · DOI
  189. [194]Bonanno G. Mariotti A. Procoli A. Folgiero V. Natale D. De Rosa L. Majolino I. Novarese L. Rocci A. Gambella M. Indoleamine 2,3-dioxygenase 1 (IDO1) activity correlates with immune system abnormalities in multiple myeloma J. Transl. Med. 2012 10 247 10.1186/1479-5876-10-247 23232072 PMC3543251 · DOI
  190. [195]Krejcik J. Casneuf T. Nijhof I.S. Verbist B. Bald J. Plesner T. Syed K. Liu K. van de Donk N.W. Weiss B.M. Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma Blood 2016 128 384 394 10.1182/blood-2015-12-687749 27222480 PMC4957162 · DOI
  191. [196]Rosenblatt J. Glotzbecker B. Mills H. Vasir B. Tzachanis D. Levine J.D. Joyce R.M. Wellenstein K. Keefe W. Schickler M. PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine J. Immunother 2011 34 409 418 10.1097/CJI.0b013e31821ca6ce 21577144 PMC3142955 · DOI
  192. [197]Yousef S. Marvin J. Steinbach M. Langemo A. Kovacsovics T. Binder M. Kröger N. Luetkens T. Atanackovic D. Immunomodulatory molecule PD-L1 is expressed on malignant plasma cells and myeloma-propagating pre-plasma cells in the bone marrow of multiple myeloma patients Blood Cancer J. 2015 5 e285 10.1038/bcj.2015.7 PMC4382668 25747678 · DOI
  193. [198]Lee B.H. Park Y. Kim J.H. Kang K.W. Lee S.J. Kim S.J. Kim B.S. PD-L1 expression in bone marrow plasma cells as a biomarker to predict multiple myeloma prognosis: Developing a nomogram-based prognostic model Sci. Rep. 2020 10 12641 10.1038/s41598-020-69616-5 32724129 PMC7387472 · DOI
  194. [199]Usmani S.Z. Schjesvold F. Oriol A. Karlin L. Cavo M. Rifkin R.M. Yimer H.A. LeBlanc R. Takezako N. McCroskey R.D. Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): A randomised, open-label, phase 3 trial Lancet Haematol. 2019 6 e448 e458 10.1016/S2352-3026(19)30109-7 31327689 · DOI · Paper page
  195. [200]Mateos M.V. Blacklock H. Schjesvold F. Oriol A. Simpson D. George A. Goldschmidt H. Larocca A. Chanan-Khan A. Sherbenou D. Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): A randomised, open-label, phase 3 trial Lancet Haematol. 2019 6 e459 e469 10.1016/S2352-3026(19)30110-3 31327687 · DOI
  196. [201]Suen H. Brown R. Yang S. Weatherburn C. Ho P.J. Woodland N. Nassif N. Barbaro P. Bryant C. Hart D. Multiple myeloma causes clonal T-cell immunosenescence: Identification of potential novel targets for promoting tumour immunity and implications for checkpoint blockade Leukemia 2016 30 1716 1724 10.1038/leu.2016.84 27102208 · DOI
  197. [202]Bailur J.K. McCachren S.S. Doxie D.B. Shrestha M. Pendleton K. Nooka A.K. Neparidze N. Parker T.L. Bar N. Kaufman J.L. Early alterations in stem-like/resident T cells, innate and myeloid cells in the bone marrow in preneoplastic gammopathy JCI Insight 2019 5 10.1172/jci.insight.127807 PMC6629164 31013254 · DOI
  198. [203]Zelle-Rieser C. Thangavadivel S. Biedermann R. Brunner A. Stoitzner P. Willenbacher E. Greil R. Jöhrer K. T cells in multiple myeloma display features of exhaustion and senescence at the tumor site J. Hematol. Oncol. 2016 9 116 10.1186/s13045-016-0345-3 27809856 PMC5093947 · DOI
  199. [204]Witzens-Harig M. Hose D. Jünger S. Pfirschke C. Khandelwal N. Umansky L. Seckinger A. Conrad H. Brackertz B. Rème T. Tumor cells in multiple myeloma patients inhibit myeloma-reactive T cells through carcinoembryonic antigen-related cell adhesion molecule-6 Blood 2013 121 4493 4503 10.1182/blood-2012-05-429415 23603913 · DOI
  200. [206]Ehrlich L.A. Chung H.Y. Ghobrial I. Choi S.J. Morandi F. Colla S. Rizzoli V. Roodman G.D. Giuliani N. IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma Blood 2005 106 1407 1414 10.1182/blood-2005-03-1080 15878977 · DOI

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Authors
García-Ortiz, A., Rodríguez-García, Y., Encinas, J., Maroto-Martín, E., Castellano, E., Teixidó, J., & Martínez-López, J.
Affiliations
  • Research Institute Hospital 12 de Octubre (ES)
  • Department of Molecular Biomedicine, Centro de Investigaciones Biológicas, CSIC, ES 28040 Madrid, Spain
  • Hematology Department, Hospital 12 de Octubre, i+12, CNIO, CIBERONC, ES 28041 Madrid, Spain
ORCID
Venue
Cancers
Publisher
MDPI AG
Published
2021-01-09
Volume
13
Issue
2
Pages
217
ISSN
2072-6694 (ISSN-L)
DOI
10.3390/cancers13020217
PMC
PMC7827690
OpenAlex
W3121051888
Cited by
238
References
233
Citations by year
2026: 39 · 2025: 50 · 2024: 45 · 2023: 44 · 2022: 42 · 2021: 18
FWCI
6.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancers (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Docta Complutense (Universidad Complutense de Madrid) (submittedVersion, cc-by)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Instituto de Salud Carlos III (ISCIII) (PI18/01519)
  • Spanish Ministry of Science, Innovation and Universities (SAF2017-85146-R)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
  • Health Sciences › Medicine › Oncology › Bone health and treatments
Keywords
multiple myeloma, tumor microenvironment, bone marrow microenvironment, bone marrow homing, mesenchymal stem cells, osteoclasts, osteoblasts, myeloid cells, lymphoid cells, immune evasion, disease progression, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, extramedullary disease, drug resistance

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