Statins in the treatment of polycythaemia vera and allied disorders: An antithrombotic and cytoreductive potential?

Leukemia Research

Volumn 30, Issue 10, 2006, Pages 1217-1225

  Hasselbalch, Hans Carl ^a   Riley, Caroline H ^a  

^a ODENSE UNIVERSITY HOSPITAL   (Denmark)

Author keywords

Antiproliferative; Antithrombotic; Polycythaemia vera; Proapoptotic; Statins

Indexed keywords

C REACTIVE PROTEIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; MEVALONIC ACID;

ADHESION; ANGIOGENESIS; ANTIANGIOGENIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; BLOOD VESSEL WALL; CHOLESTEROL SYNTHESIS; CLINICAL TRIAL; DRUG ACTIVITY; DRUG EFFECT; DRUG MECHANISM; ENZYME ACTIVITY; FIBRINOLYSIS; HUMAN; MYELOID METAPLASIA; MYELOPROLIFERATIVE DISORDER; PATHOPHYSIOLOGY; POLYCYTHEMIA VERA; PRENYLATION; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; THROMBOCYTHEMIA; THROMBOSIS; VASCULAR ENDOTHELIUM;

ANGIOGENESIS INHIBITORS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; APOPTOSIS; CELL DIVISION; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MEVALONIC ACID; MYELOPROLIFERATIVE DISORDERS; POLYCYTHEMIA VERA; THROMBOCYTHEMIA, HEMORRHAGIC;

EID: 33747144458     PISSN: 01452126     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.leukres.2005.12.018     Document Type: Article

References (153)

1. Reilly J.T. Idiopathic myelofibrosis: pathogenesis, natural history and management. Blood Rev 11 4 (1997) 233-242
2. Tefferi A. The chronic myeloproliferative disorders. Semin Hematol 36 Suppl. 2 (1999) 3-8
3. Tefferi A. Myelofibrosis with myeloid metaplasia. N Engl J Med 342 (2000) 1255-1265
4. Spivak J.L. The chronic myeloproliferative disorders: clonality and clinical heterogeneity. Semin Hematol 41 2 Suppl. 3 (2004) 1-5
5. Elliot M.A., and Tefferi A. Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol 128 (2005) 275-290
6. Finazzi G., Ruggeri M., Rodeghiero F., and Barbui T. Second malignancies in patients with essential thrombocythaemia treated with busulphan and hydroxyurea: long-term follow-up of a randomised clinical trial. Br J Haematol 110 (2000) 577-583
7. Nielsen I., and Hasselbalch H.C. Acute leukemia and myelodysplasia in patients with philadelphia chromosome negative chronic myeloproliferative disorder treated with hydroxyurea alone or with hydroxyurea after busulphan. Am J Hematol 74 (2003) 26-31
8. Finnazi G., Caruso V., Marchiola R., Capnist G., Chiesi T., Finelli C., et al. Acute leukemia in polycythemia vera. An analysis of 1,638 patients enroled in a prospective observational study. Blood 105 (2005) 2664-2670
9. Gilbert H.S. Long term treatment of myeloproliferative disease with interferon-alpha-2b: feasibility and efficacy. Cancer 83 (1998) 1205-1213
10. Bachleitner-Hofmann T., and Gisslinger H. The role of interferon-alpha in the treatment of idiopathic myelofibrosis. Ann Hematol 78 (1999) 533-538
11. Radin A.I., Kim H.T., Grant B.W., Bennett J.M., Kirkwood J.M., Stewart J.A., et al. Phase II study of alpha2 interferon in the treatment of the chronic myeloproliferative disorders. Cancer 98 (2003) 100-109
12. Birgegard G., Bjorkholm M., Kutti J., Larfars G., Lofvenberg E., Markevarn B., et al. Adverse effects and benefits of two years treatment for thrombocythemia in chronic myeloproliferative disorders. Haematologica 89 (2004) 520-527
13. Steurer M., Gastl G., Jedrzejczak W.W., Pytlik R., Lin W., Schlogl E., et al. Anagrelide for thrombocytosis in myeloproliferative disorders: a prospective study to assess efficacy and adverse event profile. Cancer 101 (2004) 2239-2246
14. Barosi G., Michelle E., Letizia C., Fillipo B., Paulo P.P., Giuseppe V., et al. Thalidomide in myelofibrosis with myeloid metaplasia: a pooled analysis of individual patient data from five studies. Leuk Lymphoma 43 (2002) 2301-2317
15. Tefferi A., Mesa R.A., Gray L.A., et al. Phase 2 trial of imatiib mesylate in myelofibrosis with myeloid metaplasia. Blood 99 (2002) 3854-3856
16. Hasselbalch H.C., Bjerrum O.W., Jensen B.A., Tøffner Clausen N., Hansen P.B., Birgens H., et al. Imatinib mesylate in idiopathic and postpolycythemic myelofibrosis. Am J Hematol 74 (2003) 238-242
17. Jones C.M., and Dickinson T.M. Polycythemia vera responds to imatinib mesylate. Am J Med Sci 325 (2003) 149-152
18. Silver R.T., and Silver R.T. Imatinib mesylate (Gleevec™) reduces phlebotomy requirements in polycythemia vera. Leukemia 17 (2003) 1186-1187
19. Hasselbalch H.C., Larsen T.S., Henriksen A.S., Christensen J.H., Hansen P.G., Pedersen N.T., et al. Imatinib mesylate in polycythemia vera. A heterogeneous response pattern but a consistent reduction in phlebotomy requirements. Blood 104 (2004) [Abstract # 4747]
20. Mesa R.A., Camoriano J.K., Geyer S.M., Kaufmann S.H., Ehrlichman C., Juckett M., et al. A phase 2 consortium (P2C) trial of R115777 (Zarnestra) in myelofibrosis with myeloid metaplasia. Blood 102 (2004) [Abstract # 3428]
21. Cortes J., Albitar M., Thomas D., Giles F., Kurzrock R., Thibault A., et al. Efficacy of the farnesyl transferase inhibitor R115777 in chronic myeloid leukemia and other hematologic malignancies. Blood 101 (2003) 1692-1697
22. Jabbour E., Kantarjian H., and Cortes J. Clinical activity of farnesyltransferase inhibitors in hematologic malignancies: possible mechanisms of action. Leuk Lymphoma 45 (2004) 2187-2195
23. Larghero J., Gervais N., Cassinat B., Rain J.D., Schlageter M.H., Padua R.A., et al. Farnesyltransferase inhibitor tipifarnib (Zarnestra R115777) preferentially inhibits in vitro autonomous erythropoiesis of polycythemia vera patient cells. Blood 105 (2005) 3743-3745
24. Newman A., Clutterbuck R.D., Powles R.L., and Millar J.L. Selective inhibition of primary acute myeloid leukaemia cell growth by simvastatin. Leukemia 8 (1994) 2023-2029
25. Newman A., Clutterbuck R.D., Powles R.L., et al. A comparison of the effect of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors simvastatin, lovastatin, and pravastatin on leukaemic and normal bone marrow progenitors. Leuk Lymphoma 24 (1997) 533-537
26. Dimitroulakos J., Nohynek D., Backway K.L., et al. Increased sensitivity of acute myeloid leukemias to lovastatin-induced apoptosis: a potential therapeutic approach. Blood 93 (1999) 1308-1318
27. Dimitroulakos J., Thai S., Wasfy G.H., Hedley D.W., Minden M.D., and Penn L.Z. Lovastatin induces a pronounced differentiation response in acute myeloid leukaemias. Leuk Lymphoma 40 (2000) 167-178
28. Xia Z., Tan M.M., Wong W.W., Dimitroulakos J., Minden M.D., and Penn L.Z. Blocking protein geranylgeranylation is essential for lovastatin-induced apoptosis of human acute myeloid leukemia cells. Leukemia 15 (2001) 1398-1407
29. Wong W.W., Tan M.M., Xia Z., Dimitroulakos J., Minden M.D., and Penn L.Z. Cerivastatin triggers tumor-specific apoptosis with higher efficacy than lovastatin. Clin Cancer Res 7 (2001) 2067-2075
30. Chapman-Shimshoni D., Yuklea M., Radney J., Shapiro H., and Lischner M. Simvastatin induces apoptosis of B-CLL cells by activation of mitochrondial caspase 9. Exp Hematol 31 (2003) 779-783
31. Kaushal V., Kohli M., and Mehta P. Potential anticancer effects of statins: facts or fiction?. Endothelium 10 (2003) 49-58
32. Chan K.K.W., Oza A.M., and Siu L.L. The statins as anticancer agents. Clin Cancer Res 9 (2003) 10-19
33. Li H.Y., Appelbaum F.R., Willman C.L., Zager R.A., and Banker D.E. Cholesterol-modulating agents kill acute myeloid leukaemia cells and sensitize them to therapeutics by blocking adaptive cholesterol responses. Blood 101 (2003) 3628-3634
34. Stirewalt D.L., Appelbaum F.R., Willman C.L., Zager R.A., and Banker D.E. Mevastatin can increase toxicity in primary AMLs exposed to standard therapeutic agents, but statin efficacy is not simply associated with ras hotspot mutations or overexpression. Leuk Res 27 (2003) 133-145
35. Grant S. Reducing cholesterol and overcoming drug resistance. Blood 104 (2004) 1598-1599
36. Banker D.E., Mayer S.J., Li H.Y., Willman C.L., Appelbaum F.R., and Zager R.A. Cholesterol synthesis and import contribute to protective cholesterol increments in acute myeloid leukaemia cells. Blood 104 (2004) 1816-1824
37. Schmidmaier R., Baumann P., Simsek M., Dayyani F., Emmerich B., and Meinhardt G. The HMG-CoA reductase inhibitor simvastatin overcomes cell-adhesion-mediated drug resistance in multiple myeloma by geranylgeranylation of Rho protein and activation of Rho kinase. Blood 104 (2004) 1825-1832
38. Graff M.R., Richel D.J., van Noorden C.J.F., and Guchelaar H.J. Effects of statins and farnesyltransferase inhibitors on the development and progression of cancer. Cancer Treat Rev 30 (2004) 609-641
39. Poynter J.N., Gruber S.B., Higgins P.D., Almog R., Bonner J.D., Rennert H.S., et al. Stains and the risk of cancer. N Engl J Med 352 (2005) 2184-2192
40. Lewis K.A., Holstein S.A., and Hohl R.J. Lovastatin alters isoprenoid biosynthetic pathway in acute myelogenous leukemia cells in vivo. Leuk Res 29 (2005) 527-533
41. Cafforio P., Dammaco F., Gernone A., and Silvestris F. Statins activate the mitochondrial pathway of apoptosis in human lymphoblasts and myeloma cells. Carcinogenesis 26 (2005) 883-891
42. Corsini A., Maggi F.M., and Catapano A.L. Pharmacology of competetive inhibitors of HMG-CoA reductase. Pharmacol Res 31 (1995) 9-27
43. Schacter M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol 1 (2005) 117-125
44. Rosenson R.S., and Tangney C.C. Anti-atherothrombotic properties of statins-implications for cardiovascular event reduction. JAMA 279 (1998) 1643-1650
45. Fenton Jr. J.W., and Shen G.X. Statins as cellular antithrombotics. Haemostasis 29 (1999) 166-169
46. Kearney D., and Fitzgerald D. The anti-thrombotic effects of statins. J Am Coll Cardiol 33 (1999) 1305-1307
47. Laufs U., Gertz K., Huang P., Nickenig G., Bohm M., Dirnagl U., et al. Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice. Stroke 31 (2000) 2437-2449
48. Lefer A.M., Scalia R., and Lefer D.J. Vascular effects of HMG CoA-reductase inhibitors (statins) unrelated to cholesterol lowering: new concepts for cardiovascular disease. Cardiovasc Res 49 (2001) 281-287
49. LaRosa J.C. Pleiotropic effects of statins and their clinical significance. Am J Cardiol 88 (2001) 291-293
50. Liao J.K. Beyond lipid lowering: the role of statins in vascular protection. Int J Cardiol 86 (2002) 5-18
51. Bonetti P.O., Lerman L.O., Napoli C., and Lerman A. Statin effects beyond lipid lowering-are they clinically relevant?. Eur Heart J 24 (2003) 225-248
52. Tekten T., Ceyhan C., Ercan E., Onbasili A.O., and Turkoglu C. The effect of atorvastatin on platelet function in patients with coronary artery disease. Acta Cardiol 59 (2004) 311-315
53. Hwang Y.S., Tsai W.C., Lu Y.H., Lin C.C., and Chen Y.F. Effect of atorvastatin on the expression of CD40 ligand and P-selectin on platelets in patients with hypercholesterolemia. Am J Cardiol 94 (2004) 364-366
54. Laufs U., Fata V.L., and Liao J.K. Inhibition of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase blocks hypoxia-mediated down-regulation of endothelial nitric oxide synthase. J Biol Chem 272 (1997) 31725-31729
55. Weis M., Heeschen C., Glassford A.J., and Cooke J.P. Statins have biphasic effects on angiogenesis. Circulation 105 (2002) 739-745
56. Ferrara D.E., and Pierangeli S.S. Diverse effects of statins on endothelial cells?. Thromb Haemost 93 (2005) 186-188
57. Musolino C., Alonci A., Allegra A., Spatari G., Bellomo G., Tringali O., et al. Increased levels of the soluble adhesion molecule E-selectin in patients with chronic myeloproliferative disorders and thromboembolic complications. Am J Hematol 57 (1998) 109-112
58. Neunteufl T., Heher S., Stefenelli T., Pabinger I., and Gisslinger H. Endothelial dysfunction in patients with polycythaemia vera. Br J Haematol 115 (2001) 354-359
59. Jensen M.K., de Nully Brown P., Thorsen S., and Hasselbalch H.C. Frequent occurrence of anticardiolipin antibodies, factor V Leiden mutation, and perturbed endothelial function in chronic myeloproliferative disorders. Am J Hematol 69 (2002) 185-191
60. Goldstein J.L., and Brown M.S. Regulation of the mevalonate pathway. Nature 343 (1990) 425-430
61. Gelb M.H. Protein prenylation, et cetera: signal transduction in two dimensions. Science 275 (1997) 1750-1751
62. Rebello A., and Martinez A. Ras proteins: recent advances and new functions. Blood 94 (1999) 2971-2980
63. Magee T., and Marshall C. New insights into the interaction of Ras with the cell membrane. Cell 98 (1999) 9-12
64. Reuter C.W., Morgan M.A., and Bergmann L. Targeting the Ras signalling pathway: a rational, mechanism-based treatment of hematologic malignancies?. Blood 96 (2000) 1655-1669
65. Bishop A.L., and Hall A. Rho GTPases and their effector proteins. Biochem J 348 (2000) 241-255
66. Park W.H., Lee Y.Y., Kim E.S., et al. Lovastatin-induced inhibition of HL-60 cell proliferation via cell cycle arrest and apoptosis. Anticancer Res 19 (1999) 3133-3140
67. Agarwal B., Bhendwal S., Halmros B., Moss S.F., Ramey W.G., and Holt P.R. Lovastatin augments apoptosis induced by chemotherapeutic agents in colon cancer cells. Clin Cancer Res 5 (1999) 2223-2229
68. Blanco-Colio L.M., Villa A., Ortego M., et al. 3-Hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors, atorvastatin and simvastatin, induce apoptosis of vascular smooth muscle cells by downregulation of Bcl-2 expression and Rho A prenylation. Atherosclerosis 161 (2002) 17-26
69. Siddals K.W., Marshman E., Westwod M., and Gibson M. Abrogation of insulin-like growth factor-I (IGF-I) and insulin action by mevalonate depletion. J Biol Chem 279 (2004) 38353-38359
70. Kureishi Y., Luo Z., Shiojima I., Bialik A., Fulton D., Lefer D.J., et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med 6 (2000) 1004-1010
71. Urbich C., Dernbach E., Zeither A.M., and Dimmeler S. Double-edged role of statins in angiogenesis signaling. Circ Res 90 (2002) 737-744
72. Vincent L., Soria C., Mirshahi F., Opolon P., Mishal Z., Vannier J.P., et al. Cerivastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibits endothelial proliferation induced by angiogenic factors in vitro and angiogenesis in in vivo models. Arterioscler Thromb Vasc Biol 22 (2002) 623-629
73. Vincent L., Albanese P., Bompais H., Uzan G., Vannier J.P., Steg P.G., et al. Insights in the molecular mechanisms of the anti-angiogenic effects of an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Thromb Haemost 89 (2003) 530-537
74. Nicosia R.F., Nicosia S.V., and Smith M. Vascular endothelial growth factor, platelet-derived growth factor, and insulin-like growth factor-1 promote rat aortic angiogenesis in vitro. Am J Pathol 145 (1994) 1023-1029
75. Warren R.S., Yuan H., Matli M.R., Ferrara N., and Donner D.B. Induction of vascular endothelial growth factor by insulin-like growth factor I in colorectal carcinoma. J Biol Chem 271 (1996) 29483-29488
76. Akagi Y., Liu W., Zebrowski B., Xie K., and Ellis L.M. Regulation of vascular endothelial growth factor expression in human colon cancer by insulin-like growth factor-I. Cancer Res 58 (1998) 4008-4014
77. Liao J.K. Effects of statins on 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition beyond low-density lipoprotein cholesterol. Am J Cardiol 96 (2005) 24F-33F
78. Notarbartolo A., Davi G., Averna M., Bargallo C.M., Ganci A., Giammarresi C., et al. Inhibition of thromboxane biosynthesis and platelet function by simvastatin in type IIa hypercholesterolemia. Arterioscler Thromb Vasc Biol 15 (1995) 247-251
79. Lijnen P., Celis H., Fagard R., Staessen J., and Amey A. Influence of cholesterol lowering on plasma membrane lipids and cationic transport systems. J Hypertens 12 (1994) 59-64
80. Malyszko J., Malyszko J.S., Hryszko T., and Mysliwiec M. Increased soluble CD40L levels are reduced by long term simvastatin in peritoneally dialyzed patients. Blood Coagul Fibrinolysis 15 (2004) 463-467
81. Lindemann S., Tolley N.D., Dixon D.A., et al. Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J Cell Biol 154 (2001) 485-490
82. Cippolone F., Mezzetti A., Porreca E., Di Febbo C., Nutini M., Fazia M., et al. Association between enhanced soluble CD40L and prothrombotic state in hypercholesterolemia: effects of statin therapy. Circulation 106 (2002) 399-402
83. Mulhaupt F., Matter C.M., Kwak B.R., Pelli G., Veillard N.R., Burger F., et al. Statins (HMG-CoA reductase inhibitors) reduce CD40 expression in human vascular cells. Cardiovasc Res 59 (2003) 755-766
84. Hwang Y.S., Tsai W.C., Lu Y.H., Lin C.C., and Chen Y.F. Effect of atorvastatin on the expression of CD40 ligand and P-selectin on platelets in patients with hypercholesterolemia. Am J Cardiol 94 (2004) 364-366
85. Mosheimer B.A., Kaneider N.C., Feistritzer C., Djanani A., Sturn D.H., Patsch J.R., et al. CD40-ligand-dependent induction of COX-2 expression in endothelial cells by activated platelets: inhibitory effects of atorvastatin. Blood Coagul Fibrinolysis 16 (2005) 105-110
86. Niwa S., Totsuka T., and Hayashi S. Inhibitory effect of fluvastatin, a HMG-CoA reductase inhibitor on the expression of adhesion molecules on human monocyte cell line. Int J Immunopharmacol 18 (1996) 669-675
87. Pruefer D., Scalia R., and Lefer A.M. Simvastatin inhibits leukocyte-endothelial cell interactions and protects against inflammatory processes in normocholesterolemic rats. Arterioscler Thromb Vasc Biol 19 (1999) 2894-2900
88. Romano M., Mezzetti A., Marulli C., et al. Fluvastatin reduces soluble P-selectin and ICAM-1 levels in hypercholestreolemic patients: role of nitric oxide. J Invest Med 48 (2000) 183-189
89. Degraeve F., Bolla M., Blaie S., et al. Modulation of COX-2 expression by statins in human aortic smooth muscle cells: involvement of geranylgeranylated proteins. J Biol Chem 276 (2001) 46849-46855
90. Eto M., and Luscher T.F. Modulation of coagulation and fibrinolytic pathways by statins. Endothelium 10 (2003) 35-41
91. Lopez S., Peiretti F., Bonardo B., Juhan-Vague I., and Nalbone G. Effect of atorvastatin and fluvastatin on the expression of plasminogen activator inhibitor type-1 in cultured human endothelial cells. Atherosclerosis 152 (2000) 359-366
92. Baetta R., Camera M., Comparato C., Altana C., Ezekowitz M.D., and Tremoli E. Fluvastatin reduces tissue factor expression and macrophage accumulation in carotid lesions of cholesterol-fed rabbits in the absence of lipid lowering. Arterioscler Thromb Vasc Biol 22 (2002) 692-698
93. Shi J., Wang J., Zheng H., Ling W., Joseph J., Li D., et al. Statins increase thrombomodulin expression and function in human endothelial cells by a mitric oxide-dependent mechanism and counteract tumor necrosis factor-alpha-induced thrombomodulin downregulation. Blood Coagul Fibrinolysis 14 (2003) 575-585
94. Lefer A.M., Campbell B., Shin Y.-K., Scalia R., Hayward R., and Lefer D.J. Simvastatin preserves the ishemic-reperfused myocardium in normocholesterolemic rat hearts. Circulation 100 (1999) 178-184
95. Ridker P.M., Rifai N., Pfeiffer M.A., Sacks F., and Braunwald E. Long-term effects of pravastatin on plasma concentrations of C-reactive protein. Circulation 100 (1999) 230-235
96. Ridker P.M., Rifai N., and Pitman Lowenthal S. Rapid reduction in C-reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia. Circulation 103 (2001) 1191-1193
97. Ridker P.M., Glynn R.J., and Hennekens C.H. C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation 97 (1998) 2007-2011
98. Koenig W., Sund M., Frohlich M., et al. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Chort Study, 1984 to 1992. Circulation 99 (1999) 237-242
99. Rohde L.E., Hennekens C.H., and Ridker P.M. Survey of C-reactive protein and cardiovascular risk factors in apparently healthy men. Am J Cardiol 84 (1999) 1018-1022
100. Ridker P.M., Hennekens C.H., Buring J.E., and Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 342 (2000) 836-843
101. Rosenson R.S., Tangney C.C., and Casey L.C. Inhibition of proinflammatory cytokine production by pravastatin. Lancet 353 (1999) 983-984
102. Mason J.C. Statins and their role in vascular protection. Clin Sci 105 (2003) 251-266
103. Reilly J.T., Nash J.R., Mackie M.J., and McVerry B.A. Endothelial cell proliferation in myelofibrosis. Br J Haematol 60 (1985) 625-630
104. Thiele J., Rompcik V., Wagner S., and Fischer R. Vascular architecture and collagen type IV in primarymyelofibrosis and polycythaemia vera: an immunomorphomeric study on trephine biopsies of bone marrow. Br J Haematol 80 (1992) 227-234
105. Lundberg L.G., Lerner R., Sundelin R., Rogers R., Folkman J., and Palmblad J. Bone marrow in polycythemia vera, chronic myelocytic leukemia and myelofibrosis has an increased vascularity. Am J Pathol 157 (2000) 15-19
106. Panteli K., Zagorianakou N., Bai M., Katsaraki A., Agnantis N.J., and Bourantas K. Angiogenesis in chronic myeloproliferative diseases detected by CD34 expression. Eur J Haematol 72 (2004) 410-415
107. Barosi G., Vittorio R., Margherita M., Luca V.G., Alessandro P., Vittorio N., et al. Spleen neoangiogenesis in patients with myelofibrosis with myeloid metaplasia. Br J Haematol 124 (2004) 618-625
108. Arora B., Ho C.L., Hoyer J.D., Mesa R.A., and Tefferi A. Bone marrow angiogenesis and its clinical correlates in myelofibrosis with myeloid metaplasia. Haematologica 89 (2004) 1454-1458
109. Castro-Malaspina H. Pathogenesis of myelofibrosis: role of ineffective megakaryopoiesis and megakaryocyte components. In: Myelofibrosis and the biology of connective tissue. New York: Alan R. Liss, Inc.; 1984. p. 427-454.
110. Le Bousse-Kerdiles M.C., and Martyre M.C. Dual implication of fibrogenic cytokines in the pathogenesis of fibrosis and myeloproliferation in myeloid metaplasia with myelofibrosis. Ann Hematol 78 (1999) 437-444
111. Raimundo F.D., Azzaro M.P., Palumbo G.A., Bagnoto S., Stagno F., Giustolisi G.M., et al. Elevated vascular endothelial growth factor (VEGF) serum levels in idiopathic myelofibrosis. Leukemia 15 (2001) 976-980
112. Murphy P., Ahmed N., and Hassan H.T. Increased serum levels of vascular endothelial growth factor correlate with splenomegaly in polycythemia vera. Leuk Res 26 (2002) 1007-1010
113. Musolino C., Calabro' L., Bellomo G., Martello F., Loteta B., Pezzano C., et al. Soluble angiogenic factors: implications for chronic myeloproliferative disorders. Am J Hematol 69 (2002) 159-163
114. Mesters R.M. Angiogenesis in hematological malignancies. Ann Hematol 81 (2002) S72-S74
115. Podar K., and Anderson K.C. The pathophysiological role of VEGF in hematological malignancies: therapeutic implications. Blood 105 (2005) 1383-1395
116. McGuire T.F., Corey S.J., and Sebti S.M. Lovastatin inhibits platelet-derived growth factor (PDGF) stimulation of phosphatidylinositol 3-kinase activity as well as association of p85 subunit to tyrosine-phosphorylated PDGF receptor. J Biol Biochem 268 (1993) 22227-22230
117. McGuire T.F., Xu X.Q., Corey S.J., Romero G.G., and Sebti S.M. Lovastatin disrupts early events in insulin signaling: a potential mechanism of lovastatin's anti-mitogenic activity. Biochem Biophys Res Commun 204 (1994) 399-406
118. Iwama A., Sawamaru M., Nara Y., and Yamori Y. Effect of lovastatin and fluoromevalonate on phosphatidylinositol 3-kinase activity stimulated with PDGF. Clin Exp Pharmacol Physiol 22 Suppl. 1 (1995) 318-320
119. Xu X.Q., McGuire T.F., Blastkovich M.A., Sebti S.M., and Romero G. Lovastatin inhibits the stimulation of mitogen-activated protein kinase by insulin in HIRcB fibroblasts. Arch Biochem Biophys 326 (1996) 233-237
120. Skaletz-Rorowski A., Muller J.G., Kroke A., et al. Lovastatin blocks basic fibroblast growth factor-induced mitogen-activated protein kinase signaling in coronary smooth muscle cells via phosphatase inhibition. Eur J Cell Biol 80 (2001) 207-212
121. Alfano D., Franso P., Vocca I., Gambi N., Pisa V., Mancini A., et al. The urokinase plasminogen activator and its receptor: role in cell growth and apoptosis. Thromb Haemost 93 (2005) 190-191
122. Zumkeller W. The insulin-like growth factor system in haematopoietic cells. Leuk Lymphoma 43 (2002) 487-491
123. LeRoith D., and Roberts C.T. The insulin-like growth factor system and cancer. Cancer Lett 195 (2003) 127-137
124. Pollak M.N., Schernhammer E.S., and Hankinson S.E. Insulin-like growth factors and neoplasia. Nat Rev 4 (2004) 505-518
125. Mitsiades C.S., Mitsiades N.S., McMullan C.J., Poulaki V., Shringarpure R., Akiyama M., et al. Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematological malignancies, and solid tumors. Cancer Cell 5 (2004) 221-230
126. Correa P.N., and Axelrrad A.A. Production of erythropoietic bursts by progenitor cells from adult human peripheral blood in an improved serum-free medium: role of insulin like growth factor I. Blood 78 (1991) 2823-2833
127. Zhang C.C., and Lodish H.F. Insulin-like growth factor 2 expressed in a novel fetal liver cell population is a growth factor for hematopoietic stem cells. Blood 103 (2004) 2513-2521
128. Correra P.N., Eskinazi D., and Axelrad A.A. Circulating erythroid progenitors in polycythemia vera are hypersensitive to insulin-like growth factor-1 in vitro: studies in an improved serum-free medium. Blood 83 (1994) 99-112
129. Mirza A.M., Ezzat S., and Axelrad A.A. Insulin-like growth factor binding protein is elevated in patients with polycythemia vera and stimulates erythroid burst formation in vitro. Blood 89 (1997) 1862-1869
130. Bock O., Tessema M., Serinsoz E., von Wasielewski R., Busche G., and Kreipe H. Aberrant expression of insulin-like growth factor-2 (IGF-2) in Philadelphia chromosome negative chronic myeloproliferative disorders. Leuk Res 28 (2004) 1145-1151
131. Baxter E.J., Scott L.M., Campbell P.J., East C., Fourouclas N., Swanton S., et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365 (2005) 1054-1061
132. James C., Ugo V., Le Couedic J.P., Staerk J., Delhommeau F., Lacout C., et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434 (2005) 1144-1148
133. Kralovics R., Passamonti F., Buser A.S., Teo S.S., Tiedt R., Passweg J.R., et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352 (2005) 1779-1790
134. Levine R.L., Wadleigh M., Cools J., Ebert B.L., Wernig G., Huntley B.J., et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocytosis, and myeloid metaplasia with myelofibrosis. Cancer Cell 7 (2005) 387-397
135. Jones AV, Kreil S, Zoi K, Waghorn K, Curtis C, Zhang L, et al. Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood 2005;106:2162-2168.
136. Parganas E., Wang D., Stravopodis D., Topham D.J., Marine J.C., Teglund S., et al. Jak2 is essential for signaling through a variety of cytokine receptors. Cell 93 (1998) 385-395
137. Reinmuth N., Fan F., Liu W., Parikh A.A., Stoeltzing O., Jung Y.D., et al. Impact of insulin-like growth factor receptor-1 function on angiogenesis, growth and metastasis of colon cancer. Lab Invest 82 (2002) 1377-1389
138. Fruchtman S.M. Treatment paradigms in the management of chronic myeloproliferative disorders. Semin Hematol 41 (2004) 18-22
139. Pucetti L., Sawamura T., Pasqui A.L., Patorelli M., Auteri A., and Bruni F. Atorvastatin reduces platelet-oxidized-LDL receptor expression in hypercholesterolaemic patients. Eur J Clin Invest 35 (2005) 47-51
140. Laufs U., La Fata V., Plutzky J., and Liao J.K. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 97 (1998) 1129-1135
141. Landolphi R., Marchioli R., Kutti J., Gisslinger H., Tognoni G., Patrono C., et al., European Collaboration on Low-Dose Aspirin in Polycythemia Vera. Efficacy and safety of low dose aspirin in polycythemia vera. N Engl J Med 350 (2004) 114-124
142. Falanga A., Marchetti M., Vignoli A., Balducci D., and Barbui T. Leucocyte-platelet interaction in patients with essential thrombocythemia and polycythemia vera. Exp Hematol 33 (2005) 523-530
143. de Gaetoano G., Cerletti C., and Evangeslista V. Recent advances in platelet-polymorphonuclear leucocyte interaction. Haemostasis 29 (1999) 41-49
144. Jensen M.K., de Nully Brown P., Lund B.V., Nielsen O.J., and Hasselbalch H.C. Increased circulating platelet-leucocyte aggregates in myeloproliferative disorders is correlated to previous thrombosis, platelet activation and platelet count. Eur J Haematol 66 (2001) 143-151
145. Kaneider N.C., Egger P., Dunzendorfer S., and Wiedermann C.J. Rho-GTPase-dependent platelet-neutrophil interaction affected by HMG-CoA reductase inhibition with altered adenosine nucleotide release and function. Arterioscler Thromb Vasc Biol 22 (2002) 1029-1035
146. Landolphi R., Ciabattoni G., Patrignani P., Castellana M.A., Pogliani E., Bizzi B., et al. Increased thromboxane biosynthesis in patients with polycythaemia vera: evidence for aspirin suppressible platelet activation in vivo. Blood 80 (1992) 1965-1971
147. Rocca B., Ciabattoni G., Tartaglione R., Cortelazzo S., Barbui T., Patrono C., et al. Increased thromboxane biosynthesis in essential thrombocythemia. Thromb Haemost 74 (1995) 1225-1230
148. Szczelik A., Musial J., Undas A., Gajewski P., Gora P., Swadazba J., et al. Inhibition of thrombin generation by simvastatin and lack of additive effects of aspirin in patients with marked hypercholesterolemia. J Am Coll Cardiol 33 (1999) 1286-1293
149. Munford R.S. Statins and the acute-phase response. N Engl J Med 344 (2001) 2016-2020
150. Ridker P.M., Rifai N., Clearfield M., Downs J.R., Weis S.E., Miles J.S., et al. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 344 (2001) 1959-1965
151. Nissen S.E., Tuzcu E.M., Schoenhagen P., Crowe T., Sasiela W.J., Tsai J., et al. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med 352 (2005) 29-38
152. Ridker P.M., Cannon C.P., Morrow D., Rifai N., Rose L.M., McCabe C.H., et al. C-reactive levels and outcomes after statin therapy. N Engl J Med 352 (2005) 20-28
153. Vincenzi B., Santini D., Avvisati G., Baldi A., La Cesa A., and Tonini G. Statins may potentiate biphosphonates anticancer properties: a new pharmacological approach?. Med Hypotheses 61 (2003) 98-101