A hostel for the hostile: The bone marrow niche in hematologic neoplasms

Haematologica

Volumn 100, Issue 11, 2015, Pages 1376-1387

  Krause, Daniela S ^a   Scadden, David T ^b  

^a INSTITUTE FOR TUMOR BIOLOGY AND EXPERIMENTAL THERAPY   (Germany)

^b MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA CATENIN; CD34 ANTIGEN; CHEMOKINE RECEPTOR CXCR4; HERMES ANTIGEN; HYPOXIA INDUCIBLE FACTOR PROLINE DIOXYGENASE; SELECTIN; STEM CELL FACTOR; STROMAL CELL DERIVED FACTOR 1; TENASCIN; TUMOR NECROSIS FACTOR ALPHA;

ACUTE LYMPHOBLASTIC LEUKEMIA; ACUTE MYELOBLASTIC LEUKEMIA; B LYMPHOCYTE; BONE MARROW; CLINICAL TRIAL (TOPIC); EXOSOME; EXTRACELLULAR MATRIX; HEMATOPOIESIS; HEMATOPOIETIC STEM CELL; HOMEOSTASIS; HUMAN; LEUKEMOGENESIS; MACROPHAGE; MYELODYSPLASTIC SYNDROME; NONHUMAN; REVIEW; TUMOR MICROENVIRONMENT; ANIMAL; HEMATOLOGIC NEOPLASMS; METABOLISM; PATHOLOGY; STEM CELL NICHE;

ANIMALS; BONE MARROW; HEMATOLOGIC NEOPLASMS; HEMATOPOIETIC STEM CELLS; HUMANS; STEM CELL NICHE; TUMOR MICROENVIRONMENT;

EID: 84946223435     PISSN: 03906078     EISSN: 15928721     Source Type: Journal    
DOI: 10.3324/haematol.2014.113852     Document Type: Review

References (134)

1. Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature. 2014;505(7483):327-334.
2. Krause DS, Scadden DT, Preffer FI. The hematopoietic stem cell niche - home for friend and foe? Cytometry B Clin Cytom. 2013;84(1):7-20.
3. Schofield R. The relationship between the spleen colony-forming cell and the haematopoietic stem cell. Blood Cells. 1978;4(1-2):7-25.
4. Knospe WH, Gregory SA, Husseini SG, Fried W, Trobaugh FE Jr. Origin and recovery of colony-forming units in locally curetted bone marrow of mice. Blood. 1972; 39(3):331-340.
5. Rafii S, Shapiro F, Pettengell R, et al. Human bone marrow microvascular endothelial cells support long-term proliferation and differentiation of myeloid and megakaryocytic progenitors. Blood. 1995;86(9):3353-3363.
6. Davis TA, Robinson DH, Lee KP, Kessler SW. Porcine brain microvascular endothelial cells support the in vitro expansion of human primitive hematopoietic bone marrow progenitor cells with a high replating potential: requirement for cell-to-cell interactions and colony-stimulating factors. Blood. 1995;85(7):1751-1761.
7. Salter AB, Meadows SK, Muramoto GG, et al. Endothelial progenitor cell infusion induces hematopoietic stem cell reconstitution in vivo. Blood. 2009;113(9):2104-2107.
8. Brandt J, Bartholemew A, Fortman J, et al. Ex vivo expansion of autologous bone marrow CD34+ cells with porcine microvascular endothelial cells results in a graft capable of rescuing lethally irradiated baboons. Blood. 1999;94(1):106-113.
9. Chute JP, Muramoto GG, Fung J, Oxford C. Soluble factors elaborated by human brain endothelial cells induce the concomitant expansion of purified human BM CD34+CD38- cells and SCID-repopulating cells. Blood. 2005;105(2):576-583.
10. Himburg HA, Muramoto GG, Daher P, et al. Pleiotrophin regulates the expansion and regeneration of hematopoietic stem cells. Nat Med. 2010;16(4):475-482.
11. Kiel MJ, Yilmaz OH, Iwashita T, et al. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005; 121(7):1109-1121.
12. Taichman RS, Reilly MJ, Emerson SG. Human osteoblasts support human hematopoietic progenitor cells in vitro bone marrow cultures. Blood. 1996; 87(2):518-524.
13. Calvi LM, Adams GB, Weibrecht KW, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003; 425(6960):841-846.
14. Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003; 425(6960):836-841.
15. Visnjic D, Kalajzic Z, Rowe DW, et al. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood. 2004;103(9):3258-3264.
16. Mendez-Ferrer S, Michurina TV, Ferraro F, et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010;466(7308):829-834.
17. 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.
18. Greenbaum A, Hsu YM, Day RB, et al. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. 2013;495(7440):227-230.
19. Ding L, Morrison SJ. Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature. 2013;495(7440):231-235.
20. Ding L, Saunders TL, Enikolopov G, Morrison SJ. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature. 2012;481(7382):457-462.
21. Kunisaki Y, Bruns I, Scheiermann C, et al. Arteriolar niches maintain haematopoietic stem cell quiescence. Nature. 2013;502(7473):637-643.
22. Winkler IG, Sims NA, Pettit AR, et al. Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood. 2010;116(23):4815-4828.
23. Chow A, Lucas D, Hidalgo A, et al. Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche. J Exp Med. 2011;208(2):261-271.
24. Gordon MY, Riley GP, Clarke D. Heparan sulfate is necessary for adhesive interactions between human early hemopoietic progenitor cells and the extracellular matrix of the marrow microenvironment. Leukemia. 1988;2(12):804-809.
25. Saez B, Ferraro F, Yusuf RZ, et al. Inhibiting stromal cell heparan sulfate synthesis improves stem cell mobilization and enables engraftment without cytotoxic conditioning. Blood. 2014;124(19):2937-2947.
26. Nakamura-Ishizu A, Okuno Y, Omatsu Y, et al. Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration. Blood. 2012;119(23):5429-5437.
27. 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.
28. Nilsson SK, Johnston HM, Whitty GA, et al. Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood. 2005;106(4):1232-1239.
29. Lévesque JP, Winkler IG, Hendy J, et al. Hematopoietic progenitor cell mobilization results in hypoxia with increased hypoxiainducible transcription factor-1 alpha and vascular endothelial growth factor A in bone marrow. Stem Cells. 2007;25(8):1954-1965.
30. Nombela-Arrieta C, Pivarnik G, Winkel B, et al. Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment. Nat Cell Biol. 2013; 15(5):533-543.
31. Parmar K, Mauch P, Vergilio JA, et al. Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proc Natl Acad Sci USA. 2007; 104(13):5431-5436.
32. Walkley CR, Olsen GH, Dworkin S, et al. A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency. Cell. 2007; 129(6): 1097-1110.
33. Walkley CR, Shea JM, Sims NA, et al. Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment. Cell. 2007;129(6):1081-1095.
34. Kim YW, Koo BK, Jeong HW, et al. Defective Notch activation in microenvironment leads to myeloproliferative disease. Blood. 2008;112(12):4628-4638.
35. Fulzele K, Krause DS, Barry K, et al. Myelopoiesis is regulated by osteocytes through Gsalpha-dependent signaling. Blood. 2013;121(6):930-939.
36. Raajimakers MH, Mukherjee S, Guo S, et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. 2010;464(7290):852-857.
37. Kode A, Manavalan JS, Mosialou I, et al. Leukaemogenesis induced by an activating b-catenin mutation in osteoblasts. Nature. 2014;506(7487):240-244.
38. Sala-Torra O, Hanna C, Loken MR, et al. Evidence of donor-derived hematologic malignancies after hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2006;12(5):511-517.
39. Blau O, Hofmann WK, 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.
40. Blau O, Baldus CD, Hofmann WK, et al. Mesenchymal stromal cells of myelodysplastic syndrome and acute myeloid leukemia patients have distinct genetic abnormalities compared with leukemic blasts. Blood. 2011;118(20):5583-5592.
41. Lesley J, Hyman R, Kincade PW. CD44 and its interaction with extracellular matrix. Adv Immunol. 1993;54:271-335.
42. Miyake K, Underhill CB, Lesley J, Kincade PW. Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition. J Exp Med. 1990; 172(1):69-75.
43. Katayama Y, Hidalgo A, Chang J, et al. CD44 is a physiological E-selectin ligand on neutrophils. J Exp Med. 2005;201(8):1183-1189.
44. Jin L, Hope KJ, Zhai Q, et al. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med. 2006; 12(10): 1167-1174.
45. Krause DS, Lazarides K, von Andrian UH, Van Etten RA. Requirement for CD44 in homing and engraftment of BCR-ABLexpressing leukemic stem cells. Nat Med. 2006;12(10):1175-1180.
46. Quéré R, Andradottir S, Brun AC, et al. High levels of the adhesion molecule CD44 on leukemic cells generate acute myeloid leukemia relapse after withdrawal of the initial transforming event. Leukemia. 2011;25 (3):515-526.
47. Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science. 1990;247(4944):824-830.
48. Li S, Ilaria RL, Million RP, et al. The P190, P210, and P230 forms of the BCR/ABL oncogene induce a similar chronic myeloid leukemia-like syndrome in mice but have different lymphoid leukemogenic activity. J Exp Med. 1999;189(9):1399-1412.
49. Krause DS, Spitzer TR, Stowell CP. The concentration of CD44 is increased in hematopoietic stem cell grafts of patients with acute myeloid leukemia, plasma cell myeloma, and non-Hodgkin lymphoma. Arch Pathol Lab Med. 2010;134(7):1033-1038.
50. Holm FL, Hellqvist E, Mason CN, et al. Malignant Reprogramming of Progenitors into Leukemia Stem Cells Is Enhanced By Upregulation of CD44 Transcript Variant 3 in Malignant Microenvironments. Blood (ASH Annual Meeting Abstracts). 2014;Abstract 511.
51. Gul-Uluda H, Valencia-Serna J, Kucharski C, et al. Polymeric nanoparticle-mediated silencing of CD44 receptor in CD34(+) acute myeloid leukemia cells. Leuk Res. 2014;38(11):1299-1308.
52. Erb U, Megaptche AP, Gu X, et al. CD44 standard and CD44v10 isoform expression on leukemia cells distinctly influences niche embedding of hematopoietic stem cells. J Hematol Oncol. 2014;7:29.
53. Singh V, Erb U, Zöller M. Cooperativity of CD44 and CD49d in leukemia cell homing, migration, and survival offers a means for therapeutic attack. J Immunol. 2013;191(10): 5304-5316.
54. Sipkins DA, Wei X, Wu JW, et al. In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. Nature. 2005;435(7044):969-973.
55. Krause DS, Lazarides K, Lewis JB, et al. Selectins and their ligands are required for homing and engraftment of BCR-ABL1+ leukemic stem cells in the bone marrow niche. Blood. 2014;123(9):1361-1371.
56. Aggoune D, Weissenberger E, Magnani JL, Van Etten RA, Krause DS. The vascular niche is involved in regulating leukemic stem cells in murine chronic myelogenous leukemia. ASH Abstract. 2014; #516.
57. Winkler IG, Barbier V, Pattabiraman DR, Gonda TJ, Magnani JL, Levesque J-P. Vascular Niche E-Selectin Protects Acute Myeloid Leukaemia Stem Cells from Chemotherapy. ASH Abstract. 2014; #620.
58. Nishioka C, Ikezoe T, Furihata M, et al. CD34/CD38 acute myelogenous leukemia cells aberrantly express CD82 which regulates adhesion and survival of leukemia stem cells. Int J Cancer. 2013;132(9):2006-2019.
59. Lundell BI, Mc Carthy JB, Kovach NL, Verfaillie CM. Activation of beta1 integrins on CML progenitors reveals cooperation between beta1 integrins and CD44 in the regulation of adhesion and proliferation. Leukemia. 1997;11(6):822-829.
60. Bhatia R, McCarthy JB, Verfaillie CM. Interferon-alpha restores normal beta 1 integrin- mediated inhibition of hematopoietic progenitor proliferation by the marrow microenvironment in chronic myelogenous leukemia. Blood. 1996;87(9):3883-3891.
61. Bhatia R, Wayner EA, McGlave PB, Verfaillie CM. Interferon-alpha restores normal adhesion of chronic myelogenous leukemia hematopoietic progenitors to bone marrow stroma by correcting impaired beta 1 integrin receptor function. J Clin Invest. 1994;94(1):384-391.
62. Becker PS, Kopecky KJ, Wilks AN, et al. Very late antigen-4 function of myeloblasts correlates with improved overall survival for patients with acute myeloid leukemia. Blood. 2009;113(4):866-874.
63. Krevvata M, Silva BC, Manavalan JS, et al. Inhibition of leukemia cell engraftment and disease progression in mice by osteoblasts. Blood. 2014;124(18):2834-2846.
64. Wei J, Wunderlich M, Fox C, et al. Microenvironment determines lineage fate in a human model of MLL-AF9 Leukemia. Cancer Cell. 2008;13(6):483-495.
65. Jin L, Tabe Y, Konoplev S, et al. CXCR4 upregulation by imatinib induces chronic myelogenous leukemia (CML) cell migration to bone marrow stroma and promotes survival of quiescent CML cells. Mol Cancer Ther. 2008;7(1):48-58.
66. Meister M, Spencer JA, Wu J, et al. The Microanatomy of the Leukemic Stem Cell Niche in Murine Chronic Myelogenous Leukemia. ASH Abstract 2014;351.
67. 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.
68. 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(2):540-550.
69. Schepers K, Pietras EM, Reynaud D, et al. Myeloproliferative neoplasia remodels the endosteal bone marrow niche into a selfreinforcing leukemic niche. Cell Stem Cell. 2013;13(3):285-299.
70. Zhang B, Ho YW, Huang Q, et al. Altered microenvironmental regulation of leukemic and normal stem cells in chronic myelogenous leukemia. Cancer Cell. 2012;21(4):577-592.
71. van den Berk LC, van der Veer A, Willemse ME, Theeuwes MJ, Luijendijk MW, Tong WH, et al. Disturbed CXCR4/CXCL12 axis in paediatric precursor B-cell acute lymphoblastic leukaemia. Br J Haematol. 2014;166(2):240-249.
72. 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.
73. Dias S, Hattori K, Zhu Z, et al. Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration. J Clin Invest. 2000;106(4):511-521.
74. Veiga JP, Costa LF, Sallan SE, et al. Leukemiastimulated bone marrow endothelium promotes leukemia cell survival. Exp Hematol. 2006;34(5):610-621.
75. Hatfield K, Oyan AM, Ersvaer E, et al. Primary human acute myeloid leukaemia cells increase the proliferation of microvascular endothelial cells through the release of soluble mediators. Br J Haematol. 2009; 144(1):53-68.
76. Aguayo A, Kantarjian H, Manshouri T, et al. Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes. Blood. 2000;96(6):2240-2245.
77. Perez-Atayde AR, Sallan SE, Tedrow U, et al. Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. Am J Path. 1997; 150(3):815-821.
78. Medyouf H, Mossner M, Jann JC, et al. Myelodysplastic cells in patients reprogram mesenchymal stromal cells to establish a transplantable stem cell niche disease unit. Cell Stem Cell. 2014;14(6):824-837.
79. Schmidt T, Kharabi Masouleh B, Loges S, et al. Loss or inhibition of stromal-derived PIGF prolongs survival of mice with imatinib- resistant Bcr-Abl1(+) leukemia. Cancer Cell. 2011;19(6):740-753.
80. Arranz L, Sanchez-Aguilera A, Martin-Perez D, et al. Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms. Nature. 2014; 512(7512):78-81.
81. Hanoun M, Zhang D, Mizoguchi T, et al. Acute myelogenous leukemia-induced sympathetic neuropathy promotes malignancy in an altered hematopoietic stem cell niche. Cell Stem Cell. 2014;15(3):365-375.
82. Frolova O, Samudio I, Benito JM, et al. Regulation of HIF-1alpha signaling and chemoresistance in acute lymphocytic leukemia under hypoxic conditions of the bone marrow microenvironment. Cancer Biol Ther. 2012;13(10):858-870.
83. Zhang H, Li H, Xi HS, Li S. HIF1 is required for survival maintenance of chronic myeloid leukemia stem cells. Blood. 2012; 119(11): 2595-2607.
84. Ng KP, Manjeri A, Lee KL, et al. Physiologic hypoxia promotes maintenance of CML stem cells despite effective BCR-ABL1 inhibition. Blood. 2014;123(21):3316-3326.
85. Gao XN, Yan F, Lin J, et al. AML1/ETO cooperates with HIF1 to promote leukemogenesis through DNMT3a transactivation. Leukemia. 2015;Mar 2 [Epub ahead of print].
86. Wang Y, Liu Y, Malek SN, et al. Targeting HIF1 eliminates cancer stem cells in hematological malignancies. Cell Stem Cell. 2011;8(4):399-411.
87. Rouault-Pierre K, Lopez-Onieva L, Foster K, et al. HIF-2alpha protects human hematopoietic stem/progenitors and acute myeloid leukemic cells from apoptosis induced by endoplasmic reticulum stress. Cell Stem Cell. 2013;13(5):549-563.
88. Jaiswal R, Luk F, Gong J, Mathys JM, Grau GE, Bebawy M. Microparticle conferred microRNA profiles--implications in the transfer and dominance of cancer traits. Mol Cancer. 2012;11:37.
89. Muralidharan-Chari V, Clancy JW, Sedgwick A, D'Souza-Schorey C. Microvesicles: mediators of extracellular communication during cancer progression. J Cell Sci.123(Pt 10):1603-1611.
90. Huan J, Hornick NI, Shurtleff MJ, et al. RNA trafficking by acute myelogenous leukemia exosomes. Cancer Res. 2013;73(2):918-929.
91. Corrado C, Raimondo S, Saieva L, et al. Exosome-mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an interleukin 8-dependent survival of leukemia cells. Cancer Lett. 2014;348(1- 2):71-76.
92. Taverna S, Amodeo V, Saieva L, et al. Exosomal shuttling of miR-126 in endothelial cells modulates adhesive and migratory abilities of chronic myelogenous leukemia cells. Mol Cancer. 2014;13:169.
93. Raimondo S, Saieva L, Corrado C, et al. Chronic myeloid leukemia-derived exosomes promote tumor growth through an autocrine mechanism. Cell Commun Signal. 2015;13:8
94. Wu JY, Purton LE, Rodda SJ, et al. Osteoblastic regulation of B lymphopoiesis is mediated by Gs{alpha}-dependent signaling pathways. Proc Natl Acad Sci USA. 2008;105(44):16976-16981.
95. Tiziani S, Kang Y, Harjanto R, et al. Metabolomics of the tumor microenvironment in pediatric acute lymphoblastic leukemia. PLoS One. 2013;8(12):e82859.
96. Conforti A, Biagini S, Del Bufalo F, et al. Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia. PLoS One. 2013;8(11):e76989.
97. Vicente Lopez A, Vazquez Garcia MN, Melen GJ, et al. Mesenchymal stromal cells derived from the bone marrow of acute lymphoblastic leukemia patients show altered BMP4 production: correlations with the course of disease. PLoS One. 2014;9(1): e84496.
98. Wang L, O'Leary H, Fortney J, Gibson LF. Ph+/VE-cadherin+ identifies a stem cell like population of acute lymphoblastic leukemia sustained by bone marrow niche cells. Blood. 2007;110(9):3334-3344.
99. Shiozawa Y, Pedersen EA, Taichman RS. GAS6/Mer axis regulates the homing and survival of the E2A/PBX1-positive B-cell precursor acute lymphoblastic leukemia in the bone marrow niche. Exp Hematol. 2010;38(2):132-140.
100. Boyerinas B, Zafrir M, Yesilkanal AE, et al. Adhesion to osteopontin in the bone marrow niche regulates lymphoblastic leukemia cell dormancy. Blood. 2013; 121(24):4821-4831.
101. de Vasconcellos JF, Laranjeira AB, Zanchin NI, et al. Increased CCL2 and IL-8 in the bone marrow microenvironment in acute lymphoblastic leukemia. Pediatr Blood Cancer. 2011;56(4):568-577.
102. Parameswaran R, Yu M, Lim M, et al. Combination of drug therapy in acute lymphoblastic leukemia with a CXCR4 antagonist. Leukemia. 2011;25(8):1314-1323.
103. Hu Z, Slayton WB. Integrin VLA-5 and FAK are Good Targets to Improve Treatment Response in the Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia. Front Oncol. 2014;4:112.
104. Joshi I, Jena N, Yoshida T, et al. Focal Adhesion Kinase Inhibitors Reverse the Stromal Adhesion Phenotype of Ikaros- Mutant B-ALL, Induce Apopotosis, and Synergize with ABL1 Tyrosine Kinase Inhibitors: A New Paradigm for Pathogenesis and Therapy of High-Risk BALL. ASH Abstract. 2014;285.
105. Ishikawa F, Yoshida S, Saito Y, et al. Chemotherapy-resistant human AML stem cells home to and engraft within the bonemarrow endosteal region. Nat Biotechnol. 2007;25(11):1315-1321.
106. Duan CW, Shi J, Chen J, et al. Leukemia propagating cells rebuild an evolving niche in response to therapy. Cancer Cell. 2014;25(6):778-793.
107. Pallasch CP, Leskov I, Braun CJ, et al. Sensitizing protective tumor microenvironments to antibody-mediated therapy. Cell. 2014;156(3):590-602.
108. Jacamo R, Chen Y, Wang Z, et al. Reciprocal leukemia-stroma VCAM-1/VLA-4-dependent activation of NF-kappaB mediates chemoresistance. Blood. 2014;123(17):2691-2702.
109. Yamamoto-Sugitani M, Kuroda J, Ashihara E, et al. Galectin-3 (Gal-3) induced by leukemia microenvironment promotes drug resistance and bone marrow lodgement in chronic myelogenous leukemia. Proc Natl Acad Sci USA. 2011; 108(42):17468-17473.
110. Fei F, Abdel-Azim H, Lim M, et al. Galectin- 3 in pre-B acute lymphoblastic leukemia. Leukemia. 2013;27(12):2385-2388.
111. Tabe Y, Jin L, Iwabuchi K, et al. Role of stromal microenvironment in nonpharmacological resistance of CML to imatinib through Lyn/CXCR4 interactions in lipid rafts. Leukemia. 2012;26(5):883-892.
112. Xia B, Tian C, Guo S, et al. c-Myc plays part in drug resistance mediated by bone marrow stromal cells in acute myeloid leukemia. Leuk Res. 2015;39(1):92-99.
113. Bewry NN, Nair RR, Emmons MF, Boulware D, Pinilla-Ibarz J, Hazlehurst LA. Stat3 contributes to resistance toward BCR-ABL inhibitors in a bone marrow microenvironment model of drug resistance. Mol Cancer Ther. 2008;7(10):3169-3175.
114. Zhang B, Li M, McDonald T, et al. Microenvironmental protection of CML stem and progenitor cells from tyrosine kinase inhibitors through N-cadherin and Wnt-beta-catenin signaling. Blood. 2013;121 (10):1824-1838.
115. Manshouri T, Estrov Z, Quintas-Cardama A, et al. Bone marrow stroma-secreted cytokines protect Jak2(V617F)-mutated cells from the effects of a JAK2 inhibitor. Cancer Res. 2011;71(11):3831-3840.
116. Hou L, Liu T, Tan J, et al. Long-term culture of leukemic bone marrow primary cells in biomimetic osteoblast niche. Int J Hematol. 2009;90(3):281-291.
117. Vaiselbuh SR, Edelman M, Lipton JM, Liu JM. Ectopic human mesenchymal stem cellcoated scaffolds in NOD/SCID mice: an in vivo model of the leukemia niche. Tissue Eng Part C Methods. 2010;16(6):1523-1531.
118. Blanco TM, Mantalaris A, Bismarck A, Panoskaltsis N. The development of a threedimensional scaffold for ex vivo biomimicry of human acute myeloid leukaemia. Biomaterials. 2010;31(8):2243-2251.
119. Tiwari A, Tursky ML, Kirkland MA, Pande G. Expansion of human hematopoietic stem/progenitor cells on decellularized matrix scaffolds. Curr Protoc Stem Cell Biol. 2014;28:Unit 1C.15.
120. Chen Y, Jacamo R, Shi YX, et al. Human extramedullary bone marrow in mice: a novel in vivo model of genetically controlled hematopoietic microenvironment. Blood. 2012;119(21):4971-4980.
121. Griessinger E, Anjos-Afonso F, Pizzitola I, et al. A niche-like culture system allowing the maintenance of primary human acute myeloid leukemia-initiating cells: a new tool to decipher their chemoresistance and selfrenewal mechanisms. Stem Cells Transl Med. 2014;3(4):520-529.
122. Aljitawi OS, Li D, Xiao Y, et al. A novel three-dimensional stromal-based model for in vitro chemotherapy sensitivity testing of leukemia cells. Leuk Lymphoma. 2014;55(2):378-391.
123. Tavor S, Eisenbach M, Jacob-Hirsch J, et al. The CXCR4 antagonist AMD3100 impairs survival of human AML cells and induces their differentiation. Leukemia. 2008;22(12): 2151-5158.
124. Nervi B, Ramirez P, Rettig MP, et al. Chemosensitization of acute myeloid leukemia (AML) following mobilization by the CXCR4 antagonist AMD3100. Blood. 2009;113(24):6206-6214.
125. Sison EA, Rau RE, McIntyre E, et al. MLLrearranged acute lymphoblastic leukaemia stem cell interactions with bone marrow stroma promote survival and therapeutic resistance that can be overcome with CXCR4 antagonism. Br J Haematol. 2013; 160(6):785-797.
126. Hoellenriegel J, Zboralski D, Maasch C, et al. The Spiegelmer NOX-A12, a novel CXCL12 inhibitor, interferes with chronic lymphocytic leukemia cell motility and causes chemosensitization. Blood. 2014;123(7): 1032-1039.
127. Agarwal A, Fleischman AG, Petersen CL, et al. Effects of plerixafor in combination with BCR-ABL kinase inhibition in a murine model of CML. Blood. 2012;120(13):2658-2668.
128. Winkler IG, Barbier V, Nowlan B, et al. Vascular niche E-selectin regulates hematopoietic stem cell dormancy, self renewal and chemoresistance. Nat Med. 2012;18(11):1651-1657.
129. Ben-Batalla I, Schultze A, Wroblewski M, et al. Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma. Blood. 2013; 122(14):2443-2452.
130. de Rooij MF, Kuil A, Geest CR, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012; 119(11):2590-2594.
131. Corrado C, Flugy AM, Taverna S, et al. Carboxyamidotriazole-orotate inhibits the growth of imatinib-resistant chronic myeloid leukaemia cells and modulates exosomes- stimulated angiogenesis. PLoS One. 2012;7(8):e42310.
132. Welner RS, Amabile G, Bararia D, et al. Treatment of chronic myelogenous leukemia by blocking cytokine alterations found in normal stem and progenitor cells. Cancer Cell. 2015;27(5):671-681.
133. Kleppe M, Kwak M, Koppikar P, et al. JAKSTAT pathway activation in malignant and nonmalignant cells contributes to MPN pathogenesis and therapeutic response. Cancer Discov. 2015;5(3):316-331.
134. Hartwell KA, Miller PG, Mukherjee S, et al. Niche-based screening identifies small-molecule inhibitors of leukemia stem cells. Nat Chem Biol. 2013;9(12):840-848.