Seminars in Oncology
Volume 33, Issue 2 , Pages 174-185 , April 2006

The Clinical and Biologic Importance of Neovascularization and Angiogenic Signaling Pathways in Chronic Lymphocytic Leukemia

  • Tait D. Shanafelt

      Affiliations

    • Corresponding Author InformationAddress correspondence to Tait D. Shanafelt, MD, Division of Hematology, The Mayo Clinic, 200 First St SW, Rochester, MN 55905.
    • ,
  • Neil E. Kay

References 

  1. Folkman J . Role of angiogenesis in tumor growth and metastasis . Semin Oncol . 2002;29:15–18
  2. Folkman J . Tumor angiogenesis (Therapeutic implications) . N Engl J Med . 1971;285:1182–1186
  3. Gimbrone MA , Leapman SB , Cotran RS , et al.   Tumor dormancy in vivo by prevention of neovascularization . J Exp Med . 1972;136:261–276
  4. Folkman J , Hanahan D . Switch to the angiogenic phenotype during tumorigenesis . Princess Takamatsu Symp . 1991;22:339–347
  5. Sugimachi K , Tanaka S , Terashi T , et al.   The mechanisms of angiogenesis in hepatocellular carcinoma (Angiogenic switch during tumor progression) . Surgery . 2002;131:S135–S141
  6. Tosetti F , Benelli R , Albini A . The angiogenic switch in solid tumors (Clinical implications) . Tumori . 2002;1(suppl):S9–S11
  7. Volpert OV , Alani RM . Wiring the angiogenic switch (Ras, Myc, and thrombospondin-1) . Cancer Cell . 2003;3:199–200
  8. Hanahan D , Weinberg RA . The hallmarks of cancer . Cell . 2000;100:57–70
  9. Mercurio AM , Bachelder RE , Bates RC , et al.   Autocrine signaling in carcinoma (VEGF and the alpha6beta4 integrin) . Semin Cancer Biol . 2004;14:115–122
  10. Brown JM . The hypoxic cell (A target for selective cancer therapy—Eighteenth Bruce F. Cain Memorial Award lecture) . Cancer Res . 1999;59:5863–5870
  11. Brizel DM , Scully SP , Harrelson JM , et al.   Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma . Cancer Res . 1996;56:941–943
  12. Hockel M , Schlenger K , Aral B , et al.   Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix . Cancer Res . 1996;56:4509–4515
  13. Dvorak HF , Nagy JA , Feng D , et al.   Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis . Curr Top Microbiol Immunol . 1999;237:97–132
  14. Robinson CJ , Stringer SE . The splice variants of vascular endothelial growth factor (VEGF) and their receptors . J Cell Sci . 2001;114:853–865
  15. Lee S , Jilani SM , Nikolova GV , et al.   Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors . J Cell Biol . 2005;169:681–691
  16. Clauss M , Weich H , Breier G , et al.   The vascular endothelial growth factor receptor Flt-1 mediates biological activities. Implications for a functional role of placenta growth factor in monocyte activation and chemotaxis . J Biol Chem . 1996;271:17629–17634
  17. Gerwins P , Skoldenberg E , Claesson-Welsh L . Function of fibroblast growth factors and vascular endothelial growth factors and their receptors in angiogenesis . Crit Rev Oncol Hematol . 2000;34:185–194
  18. Meyer M , Clauss M , Lepple-Wienhues A , et al.   A novel vascular endothelial growth factor encoded by Orf virus, VEGF-E, mediates angiogenesis via signalling through VEGFR-2 (KDR) but not VEGFR-1 (Flt-1) receptor tyrosine kinases . EMBO J . 1999;18:363–374
  19. Wise LM , Veikkola T , Mercer AA , et al.   Vascular endothelial growth factor (VEGF)-like protein from orf virus NZ2 binds to VEGFR2 and neuropilin-1 . Proc Natl Acad Sci U S A . 1999;96:3071–3076
  20. Gerber HP , McMurtrey A , Kowalski J , et al.   Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation . J Biol Chem . 1998;273:30336–30343
  21. Carmeliet P , Lampugnani MG , Moons L , et al.   Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis . Cell . 1999;98:147–157
  22. Karkkainen MJ , Petrova TV . Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymphangiogenesis . Oncogene . 2000;19:5598–5605
  23. Ross JS , Schenkein DP , Pietrusko R , et al.   Targeted therapies for cancer 2004 . Am J Clin Pathol . 2004;122:598–609
  24. Folkman J . Endogenous angiogenesis inhibitors . Apmis . 2004;112:496–507
  25. Schiffelers RM , van Rooy I , Storm G . siRNA-mediated inhibition of angiogenesis . Expert Opin Biol Ther . 2005;5:359–368
  26. Veronese ML , O’Dwyer PJ . Monoclonal antibodies in the treatment of colorectal cancer . Eur J Cancer . 2004;40:1292–1301
  27. Sandler AB , Gray R , Brahmer J , et al.   Randomized phase II/III trial of paclitaxel plus carboplatin with or without bevacizumab (NSC #704865) in patients with advanced non-squamous non-small cell lung cancer (NSCLC) (An Eastern Cooperative Oncology (ECOG) Trial -E4599) . Proc Am Soc Clin Oncol . 2005;LBA4: abstr
  28. Yang JC , Haworth L , Sherry RM , et al.   A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer . N Engl J Med . 2003;349:427–434
  29. Carmeliet P , Ferreira V , Breier G , et al.   Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele . Nature . 1996;380:435–439
  30. Ferrara N , Carver-Moore K , Chen H , et al.   Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene . Nature . 1996;380:439–442
  31. Shalaby F , Rossant J , Yamaguchi TP , et al.   Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice . Nature . 1995;376:62–66
  32. Gerber HP , Malik AK , Solar GP , et al.   VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism . Nature . 2002;417:954–958
  33. Ziegler BL , Valtieri M , Porada GA , et al.   KDR receptor (A key marker defining hematopoietic stem cells) . Science . 1999;285:1553–1558
  34. Vacca A , Ribatti D , Roncali L , et al.   Angiogenesis in B cell lymphoproliferative diseases. Biological and clinical studies . Leuk Lymphoma . 1995;20:27–38
  35. Hussong JW , Rodgers GM , Shami PJ . Evidence of increased angiogenesis in patients with acute myeloid leukemia . Blood . 2000;95:309–313
  36. Pruneri G , Bertolini F , Soligo D , et al.   Angiogenesis in myelodysplastic syndromes . Br J Cancer . 1999;81:1398–1401
  37. Lundberg LG , Lerner R , Sundelin P , et al.   Bone marrow in polycythemia vera, chronic myelocytic leukemia, and myelofibrosis has an increased vascularity . Am J Pathol . 2000;157:15–19
  38. Mesa RA , Hanson CA , Rajkumar SV , et al.   Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia . Blood . 2000;96:3374–3380
  39. 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 Pathol . 1997;150:815–821
  40. Aguayo A , Kantarjian H , Manshouri T , et al.   Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes . Blood . 2000;96:2240–2245
  41. Ridell B , Norrby K . Intratumoral microvascular density in malignant lymphomas of B-cell origin . Apmis . 2001;109:66–72
  42. Skobe M , Rockwell P , Goldstein N , et al.   Halting angiogenesis suppresses carcinoma cell invasion . Nat Med . 1997;3:1222–1227
  43. Prewett M , Huber J , Li Y , et al.   Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors . Cancer Res . 1999;59:5209–5218
  44. Folkman J . Angiogenesis and angiogenesis inhibition (An overview) . Exs . 1997;79:1–8
  45. Fiedler W , Graeven U , Ergun S , et al.   Vascular endothelial growth factor, a possible paracrine growth factor in human acute myeloid leukemia . Blood . 1997;89:1870–1875
  46. Dias S , Hattori K , Zhu Z , et al.   Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration . J Clin Invest . 2000;106:511–521
  47. Masood R , Cai J , Zheng T , et al.   Vascular endothelial growth factor/vascular permeability factor is an autocrine growth factor for AIDS-Kaposi sarcoma . Proc Natl Acad Sci U S A . 1997;94:979–984
  48. Masood R , Cai J , Zheng T , et al.   Vascular endothelial growth factor (VEGF) is an autocrine growth factor for VEGF receptor-positive human tumors . Blood . 2001;98:1904–1913
  49. Santos SC , Dias S . Internal and external autocrine VEGF/KDR loops regulate survival of subsets of acute leukemia through distinct signaling pathways . Blood . 2004;103:3883–3889
  50. Bellamy WT , Richter L , Frutiger Y , et al.   Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies . Cancer Res . 1999;59:728–733
  51. Wang L , Chen L , Benincosa J , et al.   VEGF-induced phosphorylation of Bcl-2 influences B lineage leukemic cell response to apoptotic stimuli . Leukemia . 2005;19:344–353
  52. Vacca A , Ribatti D , Roncali L , et al.   Bone marrow angiogenesis and progression in multiple myeloma . Br J Haematol . 1994;87:503–508
  53. Kumar S , Fonseca R , Dispenzieri A , et al.   Bone marrow angiogenesis in multiple myeloma (Effect of therapy) . Br J Haematol . 2002;119:665–671
  54. Rajkumar SV , Leong T , Roche PC , et al.   Prognostic value of bone marrow angiogenesis in multiple myeloma . Clin Cancer Res . 2000;6:3111–3116
  55. Vacca A , Ribatti D , Ruco L , et al.   Angiogenesis extent and macrophage density increase simultaneously with pathological progression in B-cell non-Hodgkin’s lymphomas . Br J Cancer . 1999;79:965–970
  56. Bertolini F , Paolucci M , Peccatori F , et al.   Angiogenic growth factors and endostatin in non-Hodgkin’s lymphoma . Br J Haematol . 1999;106:504–509
  57. Salven P , Teerenhovi L , Joensuu H . A high pretreatment serum vascular endothelial growth factor concentration is associated with poor outcome in non-Hodgkin’s lymphoma . Blood . 1997;90:3167–3172
  58. Salven P , Teerenhovi L , Joensuu H . A high pretreatment serum basic fibroblast growth factor concentration is an independent predictor of poor prognosis in non-Hodgkin’s lymphoma . Blood . 1999;94:3334–3339
  59. Salven P , Orpana A , Teerenhovi L , et al.   Simultaneous elevation in the serum concentrations of the angiogenic growth factors VEGF and bFGF is an independent predictor of poor prognosis in non-Hodgkin lymphoma (A single-institution study of 200 patients) . Blood . 2000;96:3712–3718
  60. Aguayo A , Estey E , Kantarjian H , et al.   Cellular vascular endothelial growth factor is a predictor of outcome in patients with acute myeloid leukemia . Blood . 1999;94:3717–3721
  61. Kumar S , Witzig TE , Dispenzieri A , et al.   Effect of thalidomide therapy on bone marrow angiogenesis in multiple myeloma . Leukemia . 2004;18:624–627
  62. Kvasnicka HM , Thiele J , Staib P , et al.   Reversal of bone marrow angiogenesis in chronic myeloid leukemia following imatinib mesylate (STI571) therapy . Blood . 2004;103:3549–3551
  63. Bertolini F , Mingrone W , Alietti A , et al.   Thalidomide in multiple myeloma, myelodysplastic syndromes and histiocytosis. Analysis of clinical results and of surrogate angiogenesis markers . Ann Oncol . 2001;12:987–990
  64. Legros L , Bourcier C , Jacquel A , et al.   Imatinib mesylate (STI571) decreases the vascular endothelial growth factor plasma concentration in patients with chronic myeloid leukemia . Blood . 2004;104:495–501
  65. Singhal S , Mehta J , Desikan R , et al.   Antitumor activity of thalidomide in refractory multiple myeloma . N Engl J Med . 1999;341:1565–1571
  66. Rajkumar SV , Fonseca R , Witzig TE , et al.   Bone marrow angiogenesis in patients achieving complete response after stem cell transplantation for multiple myeloma . Leukemia . 1999;13:469–472
  67. Kini AR , Kay NE , Peterson LC . Increased bone marrow angiogenesis in B cell chronic lymphocytic leukemia . Leukemia . 2000;14:1414–1418
  68. Molica S , Vacca A , Ribatti D , et al.   Prognostic value of enhanced bone marrow angiogenesis in early B-cell chronic lymphocytic leukemia . Blood . 2002;100:3344–3351
  69. Wolowiec D , Wozniak Z , Potoczek S , et al.   Bone marrow angiogenesis and proliferation in B-cell chronic lymphocytic leukemia . Anal Quant Cytol Histol . 2004;26:263–270
  70. Chen H , Treweeke AT , West DC , et al.   In vitro and in vivo production of vascular endothelial growth factor by chronic lymphocytic leukemia cells . Blood . 2000;96:3181–3187
  71. Molica S , Vacca A , Crivellato E , et al.   Tryptase-positive mast cells predict clinical outcome of patients with early B-cell chronic lymphocytic leukemia . Eur J Haematol . 2003;71:137–139
  72. Ribatti D , Molica S , Vacca A , et al.   Tryptase-positive mast cells correlate positively with bone marrow angiogenesis in B-cell chronic lymphocytic leukemia . Leukemia . 2003;17:1428–1430
  73. Fuhrmann-Benzakein E , Ma MN , Rubbia-Brandt L , et al.   Elevated levels of angiogenic cytokines in the plasma of cancer patients . Int J Cancer . 2000;85:40–45
  74. Banks RE , Forbes MA , Kinsey SE , et al.   Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from platelets (significance for VEGF measurements and cancer biology) . Br J Cancer . 1998;77:956–964
  75. Gora-Tybor J , Blonski JZ , Robak T . Circulating proangiogenic cytokines and angiogenesis inhibitor endostatin in untreated patients with chronic lymphocytic leukemia . Mediators Inflamm . 2003;12:167–171
  76. Duensing S , Atzpodien J . Increased intracellular and plasma levels of basic fibroblast growth factor in B-cell chronic lymphocytic leukemia . Blood . 1995;85:1978–1980
  77. Molica S , Vitelli G , Levato D , et al.   Increased serum levels of vascular endothelial growth factor predict risk of progression in early B-cell chronic lymphocytic leukaemia . Br J Haematol . 1999;107:605–610
  78. Aguayo A , O’Brien S , Keating M , et al.   Clinical relevance of intracellular vascular endothelial growth factor levels in B-cell chronic lymphocytic leukemia . Blood . 2000;96:768–770
  79. Menzel T , Rahman Z , Calleja E , et al.   Elevated intracellular level of basic fibroblast growth factor correlates with stage of chronic lymphocytic leukemia and is associated with resistance to fludarabine . Blood . 1996;87:1056–1063
  80. Molica S , Vitelli G , Levato D , et al.   Serum angiogenin is not elevated in patients with early B-cell chronic lymphocytic leukemia but is prognostic factor for disease progression . Eur J Haematol . 2004;73:36–42
  81. Fink SR , Paternoster SF , Smoley SA , et al.   Fluorescent-labeled DNA probes applied to novel biological aspects of B-cell chronic lymphocytic leukemia . Leuk Res . 2005;29:253–262
  82. Kay NE , Bone ND , Tschumper RC , et al.   B-CLL cells are capable of synthesis and secretion of both pro- and anti-angiogenic molecules . Leukemia . 2002;16:911–919
  83. Hevehan DL , Papoutsakis ET , Miller WM . Physiologically significant effects of pH and oxygen tension on granulopoiesis . Exp Hematol . 2000;28:267–275
  84. Aguayo A , Manshouri T , O’Brien S , et al.   Clinical relevance of Flt1 and Tie1 angiogenesis receptors expression in B-cell chronic lymphocytic leukemia (CLL) . Leuk Res . 2001;25:279–285
  85. Bairey O , Boycov O , Kaganovsky E , et al.   All three receptors for vascular endothelial growth factor (VEGF) are expressed on B-chronic lymphocytic leukemia (CLL) cells . Leuk Res . 2004;28:243–248
  86. Ferrajoli A , Manshouri T , Estrov Z , et al.   High levels of vascular endothelial growth factor receptor-2 correlate with shortened survival in chronic lymphocytic leukemia . Clin Cancer Res . 2001;7:795–799
  87. Lee YK , Bone ND , Strege AK , et al.   VEGF receptor phosphorylation status and apoptosis is modulated by a green tea component, epigallocatechin-3-gallate (EGCG), in B-cell chronic lymphocytic leukemia . Blood . 2004;104:788–794
  88. Lee YK , Shanafelt TD , Bone ND , et al.   VEGF receptors on chronic lymphocytic leukemia (CLL) B cells interact with STAT 1 and 3 (Implication for apoptosis resistance) . Leukemia . 2005;19:513–523
  89. Wang L , Coad JE , Fortney JM , et al.   VEGF-induced survival of chronic lymphocytic leukemia is independent of Bcl-2 phosphorylation . Leukemia . 2005;19:1486–1487
  90. Funamoto M , Fujio Y , Kunisada K , et al.   Signal transducer and activator of transcription 3 is required for glycoprotein 130-mediated induction of vascular endothelial growth factor in cardiac myocytes . J Biol Chem . 2000;275:10561–10566
  91. Niu G , Wright KL , Huang M , et al.   Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis . Oncogene . 2002;21:2000–2008
  92. Bartoli M , Gu X , Tsai NT , et al.   Vascular endothelial growth factor activates STAT proteins in aortic endothelial cells . J Biol Chem . 2000;275:33189–33192
  93. Frank DA , Mahajan S , Ritz J . B lymphocytes from patients with chronic lymphocytic leukemia contain signal transducer and activator of transcription (STAT) 1 and STAT3 constitutively phosphorylated on serine residues . J Clin Invest . 1997;100:3140–3148
  94. Liu H , Ma Y , Cole SM , et al.   Serine phosphorylation of STAT3 is essential for Mcl-1 expression and macrophage survival . Blood . 2003;102:344–352
  95. Lee Y , Bone N , Strege A , et al.   Epigallocatechin-3-gallate (EGCG) disrupts VEGF receptor-HIF (Hypoxia Inducible Factor 1-alpha) association (Implications for down-regulation of VEGF production and the induction of cell death in chronic lymphocytic luekmia (CLL) B-cells) . 2004; Proc Am Assoc Cancer Res Orlando, FL, March
  96. Gerber HP , Dixit V , Ferrara N . Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells . J Biol Chem . 1998;273:13313–13316
  97. Nor JE , Christensen J , Mooney DJ , et al.   Vascular endothelial growth factor (VEGF)-mediated angiogenesis is associated with enhanced endothelial cell survival and induction of Bcl-2 expression . Am J Pathol . 1999;154:375–384
  98. Konig A , Menzel T , Lynen S , et al.   Basic fibroblast growth factor (bFGF) upregulates the expression of bcl-2 in B cell chronic lymphocytic leukemia cell lines resulting in delaying apoptosis . Leukemia . 1997;11:258–265
  99. Bairey O , Zimra Y , Shaklai M , et al.   Bcl-2 expression correlates positively with serum basic fibroblast growth factor (bFGF) and negatively with cellular vascular endothelial growth factor (VEGF) in patients with chronic lymphocytic leukaemia . Br J Haematol . 2001;113:400–406
  100. Mateo V , Lagneaux L , Bron D , et al.   CD47 ligation induces caspase-independent cell death in chronic lymphocytic leukemia . Nat Med . 1999;5:1277–1284
  101. Rutella S , Rumi C , Puggioni P , et al.   Expression of thrombospondin receptor (CD36) in B-cell chronic lymphocytic leukemia as an indicator of tumor cell dissemination . Haematologica . 1999;84:419–424
  102. Panayiotidis P , Jones D , Ganeshaguru K , et al.   Human bone marrow stromal cells prevent apoptosis and support the survival of chronic lymphocytic leukaemia cells in vitro . Br J Haematol . 1996;92:97–103
  103. Lagneaux L , Delforge A , Bron D , et al.   Chronic lymphocytic leukemic B cells but not normal B cells are rescued from apoptosis by contact with normal bone marrow stromal cells . Blood . 1998;91:2387–2396
  104. Burger JA , Tsukada N , Burger M , et al.   Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1 . Blood . 2000;96:2655–2663
  105. Fluckiger AC , Rossi JF , Bussel A , et al.   Responsiveness of chronic lymphocytic leukemia B cells activated via surface Igs or CD40 to B-cell tropic factors . Blood . 1992;80:3173–3181
  106. Buske C , Gogowski G , Schreiber K , et al.   Stimulation of B-chronic lymphocytic leukemia cells by murine fibroblasts, IL-4, anti-CD40 antibodies, and the soluble CD40 ligand . Exp Hematol . 1997;25:329–337
  107. Kitada S , Zapata JM , Andreeff M , et al.   Bryostatin and CD40-ligand enhance apoptosis resistance and induce expression of cell survival genes in B-cell chronic lymphocytic leukaemia . Br J Haematol . 1999;106:995–1004
  108. Granziero L , Ghia P , Circosta P , et al.   Survivin is expressed on CD40 stimulation and interfaces proliferation and apoptosis in B-cell chronic lymphocytic leukemia . Blood . 2001;97:2777–2783
  109. Furman RR , Asgary Z , Mascarenhas JO , et al.   Modulation of NF-kappa B activity and apoptosis in chronic lymphocytic leukemia B cells . J Immunol . 2000;164:2200–2206
  110. Karin M , Lin A . NF-kappaB at the crossroads of life and death . Nat Immunol . 2002;3:221–227
  111. Long BW , Witte PL , Abraham GN , et al.   Apoptosis and interleukin 7 gene expression in chronic B-lymphocytic leukemia cells . Proc Natl Acad Sci U S A . 1995;92:1416–1420
  112. Kay N , Strege A , Shanafelt T , et al.   CLL B-cell interaction with bone biopsy generated marrow stromal elements enhances their apoptosis resistance in association with an angiogenic switch . Blood . 2004;104:1914a; (abstr)
  113. Farahani M , Treweeke AT , Toh CH , et al.   Autocrine VEGF mediates the antiapoptotic effect of CD154 on CLL cells . Leukemia . 2005;19:524–530
  114. Melter M , Reinders ME , Sho M , et al.   Ligation of CD40 induces the expression of vascular endothelial growth factor by endothelial cells and monocytes and promotes angiogenesis in vivo . Blood . 2000;96:3801–3808
  115. Cho CS , Cho ML , Min SY , et al.   CD40 engagement on synovial fibroblast up-regulates production of vascular endothelial growth factor . J Immunol . 2000;164:5055–5061
  116. Tai YT , Podar K , Gupta D , et al.   CD40 activation induces p53-dependent vascular endothelial growth factor secretion in human multiple myeloma cells . Blood . 2002;99:1419–1427
  117. Reinders ME , Sho M , Robertson SW , et al.   Proangiogenic function of CD40 ligand-CD40 interactions . J Immunol . 2003;1711534–1711541
  118. Till KJ , Spiller DG , Harris RJ , et al.   CLL, but not normal, B cells are dependent on autocrine VEGF and alpha4beta1 integrin for chemokine-induced motility on and through endothelium . Blood . 2005;105:4813–4819
  119. Shanafelt TD , Geyer SM , Kay NE . Prognosis at diagnosis (integrating molecular biologic insights into clinical practice for patients with CLL) . Blood . 2004;103:1202–1210
  120. Gora-Tybor J , Blonski JZ , Robak T . Cladribine decreases the level of angiogenic factors in patients with chronic lymphocytic leukemia . Neoplasma . 2002;49:145–148
  121. D’Arena G , Valente V , Vigliotti ML , et al.   Improvement of B-cell chronic lymphocytic leukemia during haemodialysis (Possible role for endogenous production of factors involved in angiogenesis and apoptosis?) . Leuk Lymphoma . 2003;44:1263–1265
  122. Shanafelt T , Geyer S , Bone N , et al.   Evaluation of the prognostic implications of pro- and anti-angiogenic cytokines in 311 patients with untreated chronic lymphocytic leukemia . Blood . 2005;106: (abstr 712)
  123. Molica S , Vitelli G , Levato D , et al.   Increased serum levels of matrix metalloproteinase-9 predict clinical outcome of patients with early B-cell chronic lymphocytic leukaemia . Eur J Haematol . 2003;70:373–378
  124. Tang Y , Nakada MT , Kesavan P , et al.   Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases . Cancer Res . 2005;65:3193–3199
  125. Podar K , Anderson KC . The pathophysiologic role of VEGF in hematologic malignancies (Therapeutic implications) . Blood . 2005;105:1383–1395
  126. Yang CS . Inhibition of carcinogenesis by tea . Nature . 1997;389:134–135
  127. Cao Y , Cao R . Angiogenesis inhibited by drinking tea . Nature . 1999;398:381
  128. Yang CS , Chen L , Lee MJ , et al.   Blood and urine levels of tea catechins after ingestion of different amounts of green tea by human volunteers . Cancer Epidemiol Biomarkers Prev . 1998;7:351–354
  129. Shanafelt TD, Lee YK, Call TG, et al: Clinical effects of oral green tea extracts in four patients with low grade b-cell malignancies. Leuk Res [e-pub Nov 2005]
  130. Chow H-HS , Cai Y , Hakim IA , et al.   Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenone in healthy individuals . Clin Cancer Res . 2003;9:3312–3319
  131. D’Amato RJ , Loughnan MS , Flynn E , et al.   Thalidomide is an inhibitor of angiogenesis . Proc Natl Acad Sci U S A . 1994;91:4082–4085
  132. Bartlett JB , Dredge K , Dalgleish AG . The evolution of thalidomide and its IMiD derivatives as anticancer agents . Nat Rev Cancer . 2004;4:314–322
  133. Rajkumar SV , Hayman S , Gertz MA , et al.   Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma . J Clin Oncol . 2002;20:4319–4323
  134. Kay N , Geyer S , Yaqoob I , et al.   Thalidomide treatment in B-chronic lymphocytic leukemia (CLL) (A North Central Cancer Treatment Group study) . Blood . 2003;102: (abstr 5162)
  135. Furman RR , Leonard JP , Allen SL , et al.   Thalidomide alone or in combination with fludarabine are effective treatmetn for patients with fludarabine-relapsed and refractory CLL . Proc Am Soc Clin Oncol . 2005; (abstr 6640)
  136. Chanan-Khan A , Miller KC , Takeshita K , et al.   Thalidomide in combination with fludarabine as initial therapy for patients (pts) with treatment requiring chronic lymphocytic leukemia (CLL) (Results of a phase I clinical trial) . Blood . 2005;106:3348–3352
  137. Richardson PG , Schlossman RL , Weller E , et al.   Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma . Blood . 2002;100:3063–3067
  138. List A , Kurtin S , Roe DJ , et al.   Efficacy of lenalidomide in myelodysplastic syndromes . N Engl J Med . 2005;352:549–557
  139. Dredge K , Horsfall R , Robinson SP , et al.   Orally administered lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro . Microvasc Res . 2005;69:56–63
  140. Miller KC , Czuczman MS , Dimiceli L , et al.   Anti-leukemic effects of novel immunimodulatory agent lenalidomide with or without rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. Encouraging preliminary results of an ongoing phase II clinical study . Proc Am Soc Clin Oncol . 2005; (abstr 6557)

PII: S0093-7754(06)00014-5

doi: 10.1053/j.seminoncol.2006.01.008

Seminars in Oncology
Volume 33, Issue 2 , Pages 174-185 , April 2006

Article Tools

* Image Usage & Resolution