Drug Resistance Updates
Volume 12, Issue 4 , Pages 103-113 , August 2009

Therapeutic targeting of microenvironmental interactions in leukemia: Mechanisms and approaches

  • Marina Konopleva

      Affiliations

    • Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, United States
    • Section of Molecular Hematology and Therapy, Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, United States
    • Corresponding Author InformationCorresponding author at: Department of Leukemia, Unit 428, M.D. Anderson Cancer Center, Holcombe blvd 1515, Houston, TX 77030, United States. Tel.: +1 713 794 1628; fax: +1 713 745 5372.
  • ,
  • Yoko Tabe

      Affiliations

    • Department of Clinical Pathology, Juntendo University School of Medicine, Tokyo, Japan
  • ,
  • Zhihong Zeng

      Affiliations

    • Section of Molecular Hematology and Therapy, Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, United States
  • ,
  • Michael Andreeff

      Affiliations

    • Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, United States
    • Section of Molecular Hematology and Therapy, Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, United States

Received 16 June 2009 ,Revised 29 June 2009 ,Accepted 29 June 2009.

References 

  1. Abkowitz JL, Robinson AE, Kale S, Long MW, Chen J. Mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure. Blood. 2003;102:1249–1253
  2. Adams GB, Chabner KT, Alley IR, Olson DP, Szczepiorkowski ZM, Poznansky MC, et al. Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature. 2006;439:599–603
  3. Adams GB, Scadden DT. The hematopoietic stem cell in its place. Nat. Immunol. 2006;7:333–337
  4. Arai F, Hirao A, Ohmura M, Sato H, Matsuoka S, Takubo K, et al. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell. 2004;118:149–161
  5. Arora A, Scholar EM. Role of tyrosine kinase inhibitors in cancer therapy. J. Pharmacol. Exp. Ther. 2005;315:971–979
  6. Avigdor A, Goichberg P, Shivtiel S, Dar A, Peled A, Samira S, et al. CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrow. Blood. 2004;103:2981–2989
  7. Blade J, Cibeira MT, Rosinol L. Bortezomib: a valuable new antineoplastic strategy in multiple myeloma. Acta Oncol. 2005;44:440–448
  8. Blau O, Hofmann WK, Baldus CD, Thiel G, Serbent V, Schümann E, et al. Chromosomal aberrations in bone marrow mesenchymal stroma cells from patients with myelodysplastic syndrome and acute myeloblastic leukemia. Exp. Hematol. 2007;35:221–229
  9. Bradstock KF, Makrynikola V, Bianchi A, Shen W, Hewson J, Gottlieb DJ. Effects of the chemokine stromal cell-derived factor-1 on the migration and localization of precursor-B acute lymphoblastic leukemia cells within bone marrow stromal layers. Leukemia. 2000;14:882–888
  10. Braun BS, Shannon K. Targeting Ras in myeloid leukemias. Clin. Cancer Res. 2008;14:2249–2252
  11. Broxmeyer HE, Cooper S, Kohli L, Hangoc G, Lee Y, Mantel C, et al. Transgenic expression of stromal cell-derived factor-1/CXC chemokine ligand 12 enhances myeloid progenitor cell survival/antiapoptosis in vitro in response to growth factor withdrawal and enhances myelopoiesis in vivo. J. Immunol. 2003;170:421–429
  12. Broxmeyer HE, Orschell CM, Clapp DW, Hangoc G, Cooper S, Plett PA, et al. Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J. Exp. Med. 2005;201:1307–1318
  13. Burger M, Hartmann T, Krome M, Rawluk J, Tamamura H, Fujii N, et al. Small peptide inhibitors of the CXCR4 chemokine receptor (CD184) antagonize the activation, migration, and antiapoptotic responses of CXCL12 in chronic lymphocytic leukemia B cells. Blood. 2005;106:1824–1830
  14. Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425:841–846
  15. Cancelas JA, Williams DA. Stem cell mobilization by beta2-agonists. Nat. Med. 2006;12:278–279
  16. Ceradini DJ, Kulkarni AR, Callaghan MJ, Tepper OM, Bastidas N, Kleinman ME, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat. Med. 2004;10:858–864
  17. Chow LQ, Eckhardt SG. Sunitinib: from rational design to clinical efficacy. J. Clin. Oncol. 2007;25:884–896
  18. Clarke DJ. Proteolysis and the cell cycle. Cell Cycle. 2002;1:233–234
  19. Colmone A, Amorim M, Pontier AL, Wang S, Jablonski E, Sipkins DA. Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells. Science. 2008;322:1861–1865
  20. Crazzolara R, Kreczy A, Mann G, Heitger A, Eibl G, Fink FM, et al. High expression of the chemokine receptor CXCR4 predicts extramedullary organ infiltration in childhood acute lymphoblastic leukaemia. Br. J. Haematol. 2001;115:545–553
  21. D’Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc. Natl. Acad. Sci. U.S.A. 1994;91:4082–4085
  22. Dazzi F, Ramasamy R, Glennie S, Jones SP, Roberts I. The role of mesenchymal stem cells in haemopoiesis. Blood Rev. 2006;20:161–171
  23. Di Raimondo F, Palumbo GA, Molica S, Giustolisi R. Angiogenesis in chronic myeloproliferative diseases. Acta Haematol. 2001;106:177–183
  24. Dialynas DP, Shao L, Billman GF, Yu J. Engraftment of human T-cell acute lymphoblastic leukemia in immunodeficient NOD/SCID mice which have been preconditioned by injection of human cord blood. Stem Cells. 2001;19:443–452
  25. Dias S, Shmelkov SV, Lam G, Rafii S. VEGF(165) promotes survival of leukemic cells by Hsp90-mediated induction of Bcl-2 expression and apoptosis inhibition. Blood. 2002;99:2532–2540
  26. Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N. Engl. J. Med. 2007;357:2123–2132
  27. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat. Med. 2003;9:669–676
  28. Fiedler W, Serve H, Döhner H, Schwittay M, Ottmann OG, O’Farrell AM, et al. A phase 1 study of SU11248 in the treatment of patients with refractory or resistant acute myeloid leukemia (AML) or not amenable to conventional therapy for the disease. Blood. 2005;105:986–993
  29. Fiegl M, Samudio I, Clise-Dwyer K, Burks JK, Mnjoyan Z, Andreeff M. CXCR4 expression and biologic activity in acute myeloid leukemia are dependent on oxygen partial pressure. Blood. 2009;113:1504–1512
  30. Garcia-Gila M, Lopez-Martin EM, Garcia-Pardo A. Adhesion to fibronectin via alpha4 integrin (CD49d) protects B cells from apoptosis induced by serum deprivation but not via IgM or Fas/Apo-1 receptors. Clin. Exp. Immunol. 2002;127:455–462
  31. Geay JF, Buet D, Zhang Y, Foudi A, Jarrier P, Berthebaud M, et al. p210BCR–ABL inhibits SDF-1 chemotactic response via alteration of CXCR4 signaling and down-regulation of CXCR4 expression. Cancer Res. 2005;65:2676–2683
  32. Heinrich MC, Blanke CD, Druker BJ, Corless CL. Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J. Clin. Oncol. 2002;20:1692–1703
  33. Holyoake TL, Jiang X, Drummond MW, Eaves AC, Eaves CJ. Elucidating critical mechanisms of deregulated stem cell turnover in the chronic phase of chronic myeloid leukemia. Leukemia. 2002;16:549–558
  34. Hussong JW, Rodgers GM, Shami PJ. Evidence of increased angiogenesis in patients with acute myeloid leukemia. Blood. 2000;95:309–313
  35. Ishibe N, Albitar M, Jilani IB, Goldin LR, Marti GE, Caporaso NE. CXCR4 expression is associated with survival in familial chronic lymphocytic leukemia, but CD38 expression is not. Blood. 2002;100:1100–1101
  36. Iwamoto S, Mihara K, Downing JR, Pui CH, Campana D. Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase. J. Clin. Invest. 2007;117:1049–1057
  37. Jazin EE, Soderstrom S, Ebendal T, Larhammar D. Embryonic expression of the mRNA for the rat homologue of the fusin/CXCR-4 HIV-1 co-receptor. J. Neuroimmunol. 1997;79:148–154
  38. Jensen PO, Mortensen BT, Hodgkiss RJ, Iversen PO, Christensen IJ, Helledie N, et al. Increased cellular hypoxia and reduced proliferation of both normal and leukaemic cells during progression of acute myeloid leukaemia in rats. Cell Prolif. 2000;33:381–395
  39. Jesenberger V, Jentsch S. Deadly encounter: ubiquitin meets apoptosis. Nat. Rev. Mol. Cell Biol. 2002;3:112–121
  40. Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat. Med. 2006;12:1167–1174
  41. Jin L, Tabe Y, Konoplev S, Xu Y, Leysath CE, Lu H, et al. CXCR4 up-regulation by imatinib induces chronic myelogenous leukemia (CML) cell migration to bone marrow stroma and promotes survival of quiescent CML cells. Mol. Cancer Ther. 2008;7:48–58
  42. Jones DL, Wagers AJ. No place like home: anatomy and function of the stem cell niche. Nat. Rev. Mol. Cell. Biol. 2008;9:11–21
  43. Juarez J, Bradstock KF, Gottlieb DJ, Bendall LJ. Effects of inhibitors of the chemokine receptor CXCR4 on acute lymphoblastic leukemia cells in vitro. Leukemia. 2003;17:1294–1300
  44. Karp JE, Gojo I, Pili R, et al. Targeting vascular endothelial growth factor for relapsed and refractory adult acute myelogenous leukemias: therapy with sequential 1-beta-d-arabiofuranosylcytosine, mitoxantrone and bevacizumab. Clin. Cancer Res. 2004;10:3577–3585
  45. Kiel MJ, Yilmaz OH, Iwashita T, Terhorst C, Morrison SJ. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005;121:1109–1121
  46. Kiel MJ, Radice GL, Morrison SJ. Lack of evidence that hematopoietic stem cells depend on N-cadherin-mediated adhesion to osteoblasts for their maintenance. Cell Stem Cell. 2007;1:204–217
  47. Kini AR, Peterson LA, Tallman MS, Lingen MW. Angiogenesis in acute promyelocytic leukemia: induction by vascular endothelial growth factor and inhibition by all-trans retinoic acid. Blood. 2001;97:3919–3924
  48. Koh MY, Spivak-Kroizman T, Venturini S, Welsh S, Williams RR, Kirkpatrick DL, et al. Molecular mechanisms for the activity of PX-478, an antitumor inhibitor of the hypoxia-inducible factor-1alpha. Mol Cancer Ther. 2008;7:90–100
  49. Kollet O, Dar A, Shivtiel S, Kalinkovich A, Lapid K, Sztainberg Y, et al. Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells. Nat. Med. 2006;12:657–664
  50. Konoplev S, Rassidakis GZ, Estey E, Kantarjian H, Liakou CI, Huang X, et al. Overexpression of CXCR4 predicts adverse overall and event-free survival in patients with unmutated FLT3 acute myeloid leukemia with normal karyotype. Cancer. 2007;109:1152–1156
  51. Konopleva M, Konoplev S, Hu W, Zaritskey AY, Afanasiev BV, Andreeff M. Stromal cells prevent apoptosis of AML cells by up-regulation of anti-apoptotic proteins. Leukemia. 2002;16:1713–1724
  52. Koomagi R, Zintl F, Sauerbrey A, Volm M. Vascular endothelial growth factor in newly diagnosed and recurrent childhood acute lymphoblastic leukemia as measured by real-time quantitative polymerase chain reaction. Clin. Cancer Res. 2001;7:3381–3384
  53. Kopp HG, Avecilla ST, Hooper AT, Rafii S. The bone marrow vascular niche: home of HSC differentiation and mobilization. Physiology (Bethesda). 2005;20:349–356
  54. Korkolopoulou P, Apostolidou E, Pavlopoulos PM, Kavantzas N, Vyniou N, Thymara , et al. Prognostic evaluation of the microvascular network in myelodysplastic syndromes. Leukemia. 2001;15:1369–1376
  55. Lapidot T, Dar A, Kollet O. How do stem cells find their way home?. Blood. 2005;106:1901–1910
  56. Lataillade JJ, Clay D, Dupuy C, Rigal S, Jasmin C, Bourin P, et al. Chemokine SDF-1 enhances circulating CD34(+) cell proliferation in synergy with cytokines: possible role in progenitor survival. Blood. 2000;95:756–768
  57. Lee K, Qian DZ, Rey S, Wei H, Liu JO, Semenza GL. Anthracycline chemotherapy inhibits HIF-1 transcriptional activity and tumor-induced mobilization of circulating angiogenic cells. Proc. Natl. Acad. Sci. U.S.A. 2009;106:2353–2358
  58. Li L, Neaves WB. Normal stem cells and cancer stem cells: the niche matters. Cancer Res. 2006;66:4553–4557
  59. Liesveld JL, Jordan CT, Phillips GL. The hematopoietic stem cell in myelodysplasia. Stem Cells. 2004;22:590–599
  60. Litz J, Krystal GW. Imatinib inhibits c-Kit-induced hypoxia-inducible factor-1alpha activity and vascular endothelial growth factor expression in small cell lung cancer cells. Mol. Cancer Ther. 2006;5:1415–1422
  61. Liu F, Wang P, Jiang X, Tan G, Qiao H, Jiang H, et al. Antisense hypoxia-inducible factor 1alpha gene therapy enhances the therapeutic efficacy of doxorubicin to combat hepatocellular carcinoma. Cancer Sci. 2008;99:2055–2061
  62. Loetscher M, Geiser T, O’Reilly T, Zwahlen R, Baggiolini M, Moser B. Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J. Biol. Chem. 1994;269:232–237
  63. Lopez-Villar O, Garcia JL, Sanchez-Guijo FM, Robledo C, Villaron EM, Hernández-Campo P, et al. Both expanded and uncultured mesenchymal stem cells from MDS patients are genomically abnormal, showing a specific genetic profile for the 5q-syndrome. Leukemia. 2009;23:664–672
  64. Ma Q, Jones D, Borghesani PR, Segal RA, Nagasawa T, Kishimoto T, et al. Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc. Natl. Acad. Sci. U.S.A. 1998;95:9448–9453
  65. Marcondes AM, Mhyre AJ, Stirewalt DL, Kim SH, Dinarello CA, Deeg HJ. Dysregulation of IL-32 in myelodysplastic syndrome and chronic myelomonocytic leukemia modulates apoptosis and impairs NK function. Proc. Natl. Acad. Sci. U.S.A. 2008;105:2865–2870
  66. Matsunaga T, Takemoto N, Sato T, Takimoto R, Tanaka I, Fujimi A, et al. Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia. Nat. Med. 2003;9:1158–1165
  67. Matsuoka S, Oike Y, Onoyama I, Iwama A, Arai F, Takubo K, et al. Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL. Genes Dev. 2008;22:986–991
  68. Mayerhofer M, Valent P, Sperr WR, Griffin JD, Sillaber C. BCR/ABL induces expression of vascular endothelial growth factor and its transcriptional activator, hypoxia inducible factor-1alpha, through a pathway involving phosphoinositide 3-kinase and the mammalian target of rapamycin. Blood. 2002;100:3767–3775
  69. McConkey DJ, Zhu K. Mechanisms of proteasome inhibitor action and resistance in cancer. Drug Resist. Updates. 2008;11:164–179
  70. Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin. Cancer Res. 2003;9:327–337
  71. Mitsiades CS, Mitsiades NS, Munshi NC, Richardson PG, Anderson KC. The role of the bone microenvironment in the pathophysiology and therapeutic management of multiple myeloma: interplay of growth factors, their receptors and stromal interactions. Eur. J. Cancer. 2006;42:1564–1573
  72. Miyake K, Medina K, Ishihara K, Kimoto M, Auerbach R, Kincade PW. A VCAM-like adhesion molecule on murine bone marrow stromal cells mediates binding of lymphocyte precursors in culture. J. Cell. Biol. 1991;114:557–565
  73. Mohle R, Failenschmid C, Bautz F, Kanz L. Overexpression of the chemokine receptor CXCR4 in B cell chronic lymphocytic leukemia is associated with increased functional response to stromal cell-derived factor-1 (SDF-1). Leukemia. 1999;13:1954–1959
  74. Mohle R, Shittenhelm M, Faienschmid C, Bautz F, Kratz-Albers K, Serve H, et al. Functional response of leukaemic blasts to stromal cell-derived factor-1 correlates with preferential expression of the chemokine receptor CXCR4 in acute myelomonocytic and lymphoblastic leukaemia. Br. J. Haematol. 2000;110:563–572
  75. Morrison SJ, Spradling AC. Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell132. 2008;598–611
  76. Mortensen BT, Jensen PO, Helledie N, Iversen PO, Ralfkiaer E, Larsen JK, et al. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats. Br. J. Haematol. 1998;102:458–464
  77. Mudry RE, Fortney JE, York T, Hall BM, Gibson LF. Stromal cells regulate survival of B-lineage leukemic cells during chemotherapy. Blood. 2000;96:1926–1932
  78. Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, et al. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature. 1996;382:635–638
  79. Naveiras O, Daley GQ. Stem cells and their niche: a matter of fate. Cell. Mol. Life Sci. 2006;63:760–766
  80. Nervi B, Ramirez P, Rettig MP, Uy GL, Holt MS, Ritchey JK, et al. Chemosensitization of AML following mobilization by the CXCR4 antagonist AMD3100. Blood. 2009;113:6206–6214
  81. Nilsson SK, Johnston HM, Coverdale JA. Spatial localization of transplanted hemopoietic stem cells: inferences for the localization of stem cell niches. Blood. 2001;97:2293–2299
  82. Nilsson SK, Johnston HM, Whitty GA, Williams B, Webb RJ, Denhardt DT, et al. Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood. 2005;106:1232–1239
  83. Ninomiya M, Abe A, Katsumi A, Xu J, Ito M, Arai F, et al. Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice. Leukemia. 2007;21:136–142
  84. Parmar K, Mauch P, Vergilio JA, Sackstein R, Down JD. Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proc. Natl. Acad. Sci. U.S.A. 2007;104:5431–5436
  85. Passegue E, Wagers AJ, Giuriato S, Anderson WC, Weissman IL. Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates. J. Exp. Med. 2005;202:1599–1611
  86. Pawson T. Regulation and targets of receptor tyrosine kinases. Eur. J. Cancer. 2002;38:S3–S10
  87. Peled A, Hardan I, Trakhtenbrot L, Gur E, Magid M, Darash-Yahana M, et al. Immature leukemic CD34+ CXCR4+ cells from CML patients have lower integrin-dependent migration and adhesion in response to the chemokine SDF-1. Stem Cells. 2002;20:259–266
  88. Perez-Atayde AR, Sallan SE, Tedrow U, Connors S, Allred E, Folkman J. Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. Am. J. Pathol. 1997;150:815–821
  89. Perry JM, Li L. Disrupting the stem cell niche: good seeds in bad soil. Cell. 2007;129:1045–1047
  90. Pruneri G, Bertolini F, Soligo D, Carboni N, Cortelezzi A, Ferrucci PF, et al. Angiogenesis in myelodysplastic syndromes. Br. J. Cancer. 1999;81:1398–1401
  91. Ptasznik A, Urbanowska E, Chinta S, Costa MA, Katz BA, Stanislaus MA, et al. Crosstalk between BCR/ABL oncoprotein and CXCR4 signaling through a Src family kinase in human leukemia cells. J. Exp. Med. 2002;196:667–678
  92. Qiang YW, Chen Y, Stephens O, Brown N, Chen B, Epstein J, et al. Myeloma-derived Dickkopf-1 disrupts Wnt-regulated osteoprotegerin and RANKL production by osteoblasts: a potential mechanism underlying osteolytic bone lesions in multiple myeloma. Blood. 2008;112:196–207
  93. Raab, M.S., Podar, K., Breitkreutz, I., Richardson, P.G., Anderson, K.C., 2009. Multiple myeloma. Lancet doi:10.1016/S0140-6736(09)60221-x.
  94. Rajkumar SV, Leong T, Roche PC, Fonseca R, Dispenzieri A, Lacy MQ, et al. Prognostic value of bone marrow angiogenesis in multiple myeloma. Clin. Cancer Res. 2000;6:3111–3116
  95. Ramasamy R, Lam EW, Soeiro I, Tisato V, Bonnet D, Dazzi F. Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells: impact on in vivo tumor growth. Leukemia. 2007;21:304–310
  96. Richardson PG, Schlossman RL, Weller E, Hideshima T, Mitsiades C, Davies F, et al. Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood. 2002;100:3063–3067
  97. Richardson PG, Mitsiades C, Hideshima T, Anderson KC. Bortezomib: proteasome inhibition as an effective anticancer therapy. Annu. Rev. Med. 2006;57:33–47
  98. Roccaro AM, Hideshima T, Raje N, Kumar S, Ishitsuka K, Yasui H, et al. Bortezomib mediates antiangiogenesis in multiple myeloma via direct and indirect effects on endothelial cells. Cancer Res. 2006;66:184–191
  99. Rombouts EJ, Pavic B, Löwenberg B, Ploemacher RE. Relation between CXCR-4 expression, Flt3 mutations, and unfavorable prognosis of adult acute myeloid leukemia. Blood. 2004;104:550–557
  100. Rupec RA, Jundt F, Rebholz B, Eckelt B, Weindl G, Herzinger T, et al. Stroma-mediated dysregulation of myelopoiesis in mice lacking I kappa B alpha. Immunity. 2005;22:479–491
  101. Sacchetti B, Funari A, Michienzi S, Di Cesare S, Piersanti S, Saggio I, et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell. 2007;131:324–336
  102. Salgia R, Quackenbush E, Lin J, Souchkova N, Sattler M, Ewaniuk DS, et al. The BCR/ABL oncogene alters the chemotactic response to stromal-derived factor-1alpha. Blood. 1999;94:4233–4246
  103. Schmidt-Arras D, Schwable J, Bohmer FD, Serve H. Flt3 receptor tyrosine kinase as a drug target in leukemia. Curr. Pharm. Des. 2004;10:1867–1883
  104. Shen W, Bendall LJ, Gottlieb DJ, Bradstock KF. The chemokine receptor CXCR4 enhances integrin-mediated in vitro adhesion and facilitates engraftment of leukemic precursor-B cells in the bone marrow. Exp. Hematol. 2001;29:1439–1447
  105. Shojaei F, Ferrara N. Role of the microenvironment in tumor growth and in refractoriness/resistance to-anti-angiogenic therapies. Drug Resist. Updates. 2008;11:219–230
  106. Sipkins DA, Wei X, Wu JW, Runnels JM, Côté D, Means TK, et al. In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. Nature. 2005;435:969–973
  107. Staller P, Sulitkova J, Lisztwan J, Moch H, Oakeley EJ, Krek W. Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL. Nature. 2003;425:307–311
  108. Strieter RM. Masters of angiogenesis. Nat. Med. 2005;11:925–927
  109. 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;25:977–988
  110. Tabe Y, Jin L, Tsutsumi-Ishii Y, Xu Y, McQueen T, Priebe W, et al. Activation of integrin-linked kinase is a critical prosurvival pathway induced in leukemic cells by bone marrow-derived stromal cells. Cancer Res. 2007;67:684–694
  111. Trisciuoglio D, Iervolino A, Zupi G, Del Bufalo D. Involvement of PI3K and MAPK signaling in bcl-2-induced vascular endothelial growth factor expression in melanoma cells. Mol. Biol. Cell. 2005;16:4153–4162
  112. Turley EA, Noble PW, Bourguignon LY. Signaling properties of hyaluronan receptors. J. Biol. Chem. 2002;277:4589–4592
  113. Vacca A, Ribatti D, Presta M, Minischetti M, Iurlaro M, Ria R, et al. Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. Blood. 1999;93:3064–3073
  114. Veschini L, Belloni D, Foglieni C, Cangi MG, Ferrarini M, Caligaris-Cappio F, et al. Hypoxia-inducible transcription factor-1 alpha determines sensitivity of endothelial cells to the proteosome inhibitor bortezomib. Blood. 2007;109:2565–2570
  115. Voermans C, van Heese WP, de Jong I, Gerritsen WR, van der Schoot CE. Migratory behavior of leukemic cells from acute myeloid leukemia patients. Leukemia. 2002;16:650–657
  116. Walkley CR, Shea JM, Sims NA, Purton LE, Orkin SH. Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment. Cell. 2007;129:1081–1095
  117. Walkley CR, Olsen GH, Dworkin S, Fabb SA, Swann J, McArthur GA, et al. A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency. Cell. 2007;129:1097–1110
  118. Wang M, Dimopoulos MA, Chen C, Cibeira MT, Attal M, Spencer A, et al. Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure. Blood. 2008;112:4445–4451
  119. Warner JK, Wang JC, Hope KJ, Jin L, Dick JE. Concepts of human leukemic development. Oncogene. 2004;23:7164–7177
  120. Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N. Engl. J. Med. 2007;357:2133–2142
  121. Weisberg E, Barrett R, Liu Q, Stone R, Gray N, Griffin JD. FLT3 inhibition and mechanisms of drug resistance in mutant FLT3-positive AML. Drug Resist. Updates. 2009;12:81–89
  122. Wellmann S, Guschmann M, Griethe W, Eckert C, von Stackelberg A, Lottaz C, et al. Activation of the HIF pathway in childhood ALL, prognostic implications of VEGF. Leukemia. 2004;18:926–933
  123. Wight TN, Kinsella MG, Keating A, Singer JW. Proteoglycans in human long-term bone marrow cultures: biochemical and ultrastructural analyses. Blood. 1986;67:1333–1343
  124. Xie Y, Yin T, Wiegraebe W, He XC, Miller D, Stark D, et al. Detection of functional haematopoietic stem cell niche using real-time imaging. Nature. 2009;457:97–101
  125. Yilmaz OH, Valdez R, Theisen BK, Guo W, Ferguson DO, Wu H, et al. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature. 2006;441:475–482
  126. Zahiragic L, Schliemann C, Bieker R, et al. Bevacizumab reduces VEGF expression in patients with relapsed and refractory acute myeloid leukemia without clinical antileukemic activity. Leukemia. 2007;21:1310–1312
  127. Zeng Z, Shi YX, Samudio IJ, Wang RY, Ling X, Frolova O, et al. Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML. Blood. 2009;113:6215–6224
  128. Zhang J, Niu C, Ye L, Huang H, He X, Tong WG, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425:836–841
  129. Zhang J, Wang J, Liu Y, Sidik H, Young KH, Lodish HF, et al. Oncogenic K-ras-induced leukemogeneis: hematopoietic stem cells as the initial target and lineage-specific progenitors as the potential targets for final leukemic transformation. Blood. 2009;113:1304–1314
  130. Zuckerman KS, Wicha MS. Extracellular matrix production by the adherent cells of long-term murine bone marrow cultures. Blood. 1983;61:540–547

PII: S1368-7646(09)00047-8

doi: 10.1016/j.drup.2009.06.001

Drug Resistance Updates
Volume 12, Issue 4 , Pages 103-113 , August 2009