Abstract
Hepatocyte growth factor (HGF) is a potent angiogenic factor. The aim of our study was to evaluate plasma HGF levels and their prognostic significance in patients with newly diagnosed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The sandwich enzyme immunoassay technique was used to quantify HGF in stored samples obtained before treatment from patients with AML (59 patients) and MDS (42 patients) treated at The University of Texas MD Anderson Cancer Center. HGF levels were significantly higher in patients with AML or MDS than in healthy individuals (P < 0.0001). Higher HGF levels in both AML and MDS correlated significantly with white blood cell (P = 0.000001 for both groups) and monocyte counts (P = 0.0004 and 0.003, respectively), and with poor performance status (P = 0.03 and 0.001, respectively). Using Cox proportional hazard model and HGF levels as a continuous variable, plasma levels of HGF correlated with shorter survival of AML (P = 0.001), but not MDS (P = 0.34) patients. No significant correlation was observed between HGF levels and complete remission rate or duration. In the multivariate analysis HGF retained its significance as prognostic factor in AML (P = 0.02), along with age (P = 0.0005).
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References
Vacca A, Ribatti D, Roncali L, Ranieri G, Serio G, Silvestris F, Dammacco F . Bone marrow angiogenesis and progression in multiple myeloma Br J Haematol 1994 87: 503–508
Vacca A, Ribatti D, Presta M, Minischetti M, Iurlaro M, Ria R, Albini A, Bussolino F, Dammacco F . Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma Blood 1999 93: 3064–3073
Vacca A, Di Loreto M, Ribatti D, Di Stefano R, Gadaleta-Caldarola G, Iodice G, Caloro D, Dammacco F . Bone marrow of patients with active multiple myeloma: angiogenesis and plasma cell adhesion molecules LFA-1, VLA-4, LAM-1, and CD44 Am J Hematol 1995 50: 9–14
Ribatti D, Vacca A, Nico B, Quondamatteo F, Ria R, Minischetti M, Marzullo A, Herken R, Roncali L, Dammacco F . Bone marrow angiogenesis and mast cell density increase simultaneously with progression of human multiple myeloma Br J Cancer 1999 79: 451–455
Ribatti D, Vacca A, Nico B, Fanelli M, Roncali L, Dammacco F . Angiogenesis spectrum in the stroma of B-cell non-Hodgkin's lymphomas. An immunohistochemical and ultrastructural study Eur J Haematol 1996 56: 45–53
Ribatti D, Nico B, Vacca A, Marzullo A, Calvi N, Roncali L, Dammacco F . Do mast cells help to induce angiogenesis in B-cell non-Hodgkin's lymphomas? Br J Cancer 1998 77: 1900–1906
Vacca A, Ribatti D, Ruco L, Giacchetta F, Nico B, Quondamatteo F, Ria, R Iurlaro M, Dammacco F . Angiogenesis extent and macrophage density increase simultaneously with pathological progression in B-cell non-Hodgkin's lymphomas Br J Cancer 1999 79: 965–970
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
Pruneri G, Bertolini F, Soligo D, Carboni N, Cortelezzi A, Ferrucci PF, Buffa R, Lambertenghi-Deliiers G, Pezzella F . Angiogenesis in myelodysplastic syndromes Br J Cancer 1999 81: 1398–1401
Lundberg LG, Lerner R, Sundelin P, Rogers R, Folkman J, Palmblad J . Bone marrow in polycythemia vera, chronic myelocytic leukemia, and myelofibrosis has an increased vascularity Am J Pathol 2000 157: 15–19
Hussong JW, Rodgers GM, Shami PJ . Evidence of increased angiogenesis in patients with acute myeloid leukemia Blood 2000 95: 309–313
Aguayo A, Kantarjian H, Manshouri T, Gidel C, Estey E, Thomas D, Koller C, Estrov Z, O'Brien S, Keating M, Frieriech E, Albitar M . Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes Blood 2000 96: 2240–2245
Jones A, Harris AL . New developments in angiogenesis: a major mechanism for tumor growth and target for therapy Cancer J Sci Am 1998 4: 209–217
Gruber G, Schwarzmeier JD, Shehata M, Hilgarth M, Berger R . Basic fibroblast growth factor is expressed by CD19/CD11c-positive cells in hairy cell leukemia Blood 1999 94: 1077–1185
Fiedler W, Graeven U, Ergun S, Verago S, Kilic N, Stockschlader M, Hossfeld DK . Vascular endothelial growth factor, a possible paracrine growth factor in human acute myeloid leukemia Blood 1997 89: 1870–1875
Aguayo A, O'Brien S, Keating M, Manshouri T, Gidel C, Barlogie B, Beran M, Koller C, Kantarjian H, Albitar M . Clinical relevance of intracellular vascular endothelial growth factor levels in B-cell chronic lymphocytic leukemia Blood 2000 96: 768–770
Aguayo A, Estey E, Kantarjian H, Manshouri T, Gidel C, Keating M, Giles F, Estrov Z, Barlogie B, Albitar M . Cellular vascular endothelial growth factor is a predictor of outcome in patients with acute myeloid leukemia Blood 1999 94: 3717–3721
Bussolino F, Di Renzo MF, Ziche M, Bocchietto E, Olivero M, Naldini L, Gaudino G, Tamagnone L, Coffer A, Comoglio PM . Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth J Cell Biol 1992 119: 629–641
Grant DS, Kleinman HK, Goldberg ID, Bhargava MM, Nickoloff BJ, Kinsella JL, Polverini P, Rosen EM . Scatter factor induces blood vessel formation in vivo Proc Natl Acad Sci USA 1993 90: 1937–1941
Morimoto A, Tada K, Nakayama Y, Kohno K, Naito S, Ono M, Kuwano M . Cooperative roles of hepatocyte growth factor and plasminogen activator in tubular morphogenesis by human microvascular endothelial cells Jpn J Cancer Res 1994 85: 53–62
Jiang W, Hiscox S, Matsumoto K, Nakamura T . Hepatocyte growth factor/scatter factor, its molecular, cellular and clinical implications in cancer Crit Rev Oncol Hematol 1999 29: 209–248
Roletto F, Galvani AP, Cristiani C, Valsasina B, Landonio A, Bertolero F . Basic fibroblast growth factor stimulates hepatocyte growth factor/scatter factor secretion by human mesenchymal cells J Cell Physiol 1996 166: 105–111
Van Belle E, Witzenbichler B, Chen D, Silver M, Chang L, Schwall R, Isner JM . Potentiated angiogenic effect of scatter factor/hepatocyte growth factor via induction of vascular endothelial growth factor: the case for paracrine amplification of angiogenesis Circulation 1998 97: 381–390
To CT, Tsao MS . The roles of hepatocyte growth factor/scatter factor and met receptor in human cancers Oncol Rep 1998 5: 1013–1024
Abounader R, Ranganathan S, Lal B, Fielding K, Book A, Dietz H, Burger P, Laterra J . Reversion of human glioblastoma malignancy by U1 small nuclear RNA/ribozyme targeting of scatter factor/hepatocyte growth factor and c-met expression J Natl Cancer Inst 1999 91: 1548–1556
Date K, Matsumoto K, Kuba K, Shimura H, Tanaka M, Nakamura T . Inhibition of tumor growth and invasion by a four-kringle antagonist (HGF/NK4) for hepatocyte growth factor Oncogene 1998 17: 3045–3054
Seidel C, Borset M, Turesson I, Abildgaard N, Sundan A, Waage A . Elevated serum concentrations of hepatocyte growth factor in patients with multiple myeloma. The Nordic Myeloma Study Group Blood 1998 91: 806–812
Borset M, Hjorth-Hansen H, Seidel C, Sundan A, Waage A . Hepatocyte growth factor and its receptor c-met in multiple myeloma Blood 1996 88: 3998–4004
Borset M, Seidel C, Hjorth-Hansen H, Waage A, Sundan A . The role of hepatocyte growth factor and its receptor c-Met in multiple myeloma and other blood malignancies Leuk Lymphoma 1999 32: 249–256
Estey E, Thall P, Beran M, Kantarjian H, Pierce S, Keating M . Effect of diagnosis (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukemia (AML)) on outcome of AML-type chemotherapy Blood 1997 90: 2969–2977
Pons E, Uphoff CC, Drexler HG . Expression of hepatocyte growth factor and its receptor c-met in human leukemia-lymphoma cell lines Leuk Res 1998 22: 797–804
Nakamura S, Gohda E, Matsunaga T, Yamamoto I, Minowada J . Production of hepatocyte growth factor by human haematopoietic cell lines Cytokine 1994 6: 285–294
Nakamura S, Gohda E, Matsuo Y, Yamamoto I, Minowada J . Significant amount of hepatocyte growth factor detected in blood and bone marrow plasma of leukaemia patients Br J Haematol 1994 87: 640–642
Hino M, Inaba M, Goto H, Nishizawa Y, Tatsumi N, Nishino T, Morii H . Hepatocyte growth factor levels in bone marrow plasma of patients with leukaemia and its gene expression in leukaemic blast cells Br J Cancer 1996 73: 119–123
Hjorth-Hansen H, Seidel C, Lamvik J, Borset M, Sundan A, Waage A . Elevated serum concentrations of hepatocyte growth factor in acute myelocytic leukaemia Eur J Haematol 1999 62: 129–134
Banks RE, Forbes MA, Kinsey SE, Stanley A, Ingham E, Walters C, Selby PJ . 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
Russell WE, McGowan JA, Bucher NL . Partial characterization of a hepatocyte growth factor from rat platelets J Cell Physiol 1984 119: 183–192
Strain AJ, McGowan JA, Bucher NL . Stimulation of DNA synthesis in primary cultures of adult rat hepatocytes by rat platelet-associated substance(s) In Vitro 1982 18: 108–116
Sakon M, Kita Y, Takeda Y, Higaki N, Ohzato H, Umeshita K, Hasuike Y, Gotoh M, Monden M . Measurement of hepatocyte growth factor in serum and plasma Int J Clin Lab Res 1999 29: 110–113
Weimar IS, Voermans C, Bourhis JH, Miranda N, van den Berk PC, Nakamura T, de Gast GC, Gerritsen WR . Hepatocyte growth factor/scatter factor (HGF/SF) affects proliferation and migration of myeloid leukemic cells Leukemia 1998 12: 1195–1203
Beilmann M, Odenthal M, Jung W, Vande Woude GF, Dienes HP, Schirmacher P . Neo-expression of the c-met/hepatocyte growth factor-scatter factor receptor gene in activated monocytes Blood 1997 90: 4450–4458
Fuhrmann-Benzakein E, Ma MN, Rubbia-Brandt L, Mentha G, Ruefenacht D, Sappino AP, Pepper MS . Elevated levels of angiogenic cytokines in the plasma of cancer patients Int J Cancer 2000 85: 40–45
Anderlini A, Luna M, Kantarjian HM, O'Brien S, Pierce S, Keating MJ, Estey EH . Causes of initial remission induction failure in patients with acute myeloid leukemia and myelodysplastic syndrome Leukemia 1996 10: 600–608
Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeddis J, Barlogie B . Antitumor activity of thalidomide in refractory multiple myeloma New Engl J Med 1999 341: 1565–1571
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SV is supported by grant T32-CA09666 from the National Institute of Health, USA.
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Verstovsek, S., Kantarjian, H., Estey, E. et al. Plasma hepatocyte growth factor is a prognostic factor in patients with acute myeloid leukemia but not in patients with myelodysplastic syndrome. Leukemia 15, 1165–1170 (2001). https://doi.org/10.1038/sj.leu.2402182
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DOI: https://doi.org/10.1038/sj.leu.2402182
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