Abstract
Aim
Angiogenesis is the formation of new blood vessels from preexisting one. The angiopoietins act a central role in these process. The aim of the present study is to the assess the impact of the circulating levels of angiopoietin-1 (Angi-1), Angiopoietin-2 (Angi-2), soluble Tie2 receptor (sTie2), and calculated Angi-2/sTie2 ratio on overall survival in 71 acute myeloid leukemia patients and 19 normal controls.
Materials and methods
Ang-2, and calculated angi-2/sTie values were significantly higher in AML patients as compared to healthy volunteer (P= 0.002, 0.015 respectively) on the other hand Angi-1 was not significantly different in patients and control.
Results
In univariate Cox proportional hazards model Angi-2, sTie2, angi-2/sTie2 ratio were predictive of poor survival. In multivariate analysis the calculated angi-2/sTie2 ratio is independent prognostic factor, with relative risk of 3.939, with 95% confidence interval 0.002–0.001.
Conclusion
The calculated angiopoietin-2/sTie2 ratio represent an independent prognostic factor in AML and its value should be considered when considering anti angiogenic therapy.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Stone RM, O’Donnell MR, Sekeres MA (2004) Acute myeloid leukaemia. Hematology (Am Soc Hematol Educ Program) 1:98–117
Takakura N, Watanabe T, Suenobu S, Vamada Y, Noda T, Ito Y et al. (2000) A role for hematopoitic stem cells in promiting angiogenesis. Cell 102: 199–209
Risau W (1997) Mechanisms of angiogenesis. Nature 386:671–674
Santos SC, Dias S (2004). lnternal and external autocrine VEGF/KDR loops regulate survival of subsets of acute leukemia through distinct signaling pathways. Blood 103:3883–3889
Bieker R, Padro T, Kramer J, Steins M, Kessler T, Retzlaff S et al. (2003) Overexpression of basic fibroblast growth factor and autocrine stimulation in acute myeloid leukemia. Cancer Res 63:7241–7246
Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C et al. (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277:55–60
Sato A, Iwama A, Takakura N, Nishio H, Yancopoulos GO, Suda T (1998) Characterization of TEK receptor tyrosine kinase and its ligands, is Angiopoietins, in human hematopoietic progenitor cells. Int lmmunol 10:1217–1227
Wizenbichler B, Maisonpierre PC, Jones P, Yancopoulos GD, Isner JM (1998) Chemotactic properties of angiopoietin-1 and -2, ligands for the endothelial-specific receptor tyrosine kinase Tie2. J Biol Chem 273:78514–78521
Hanahan D (1997) Signaling vascular morphogenesis and maintenance. Science 277:48–50
Tait CR, Jones PF (2004) Angiopoietins in tumours: the angiogenic switch. J Pathol 204:1–10
Loges S, Heil G, Bruweleit M, Schoder V, Butzal M, Fischer U et al. (2005) Analysis of concerted expression of angiogenic growth factors in acute myeloid leukemia: expression of angiopoietin-2 represents an independent prognostic factor for overall survival. J Clin Oncol 23: 1109–1117
Quartarone E, Alonci A, Allegra A, Bellomo G, Calabro L, D’Angelo A et al. (2006) Differential levels of soluble angiopoietin-2 and Tie-2 in patients with haematological malignancies. Eur J Haematol 77:480–485
Schliemann C, Bieker R, Padro T, Kessler T, Hintelmann H, Buchner T, Berdel WE, Mesters RM (2007) Expression of angiopoietins and their receptor Tie2 in the bone marrow of patients with acute myeloid leukemia. Haematologica 91: 1203–1211
Schliemann C, Bieker R, Thoennissen N, Gerss J, Liersch R, Kessler T, Büchner T, Berdel WE, Mesters RM (2007) Circulating angiopoietin-2 is a strong prognostic factor in acute myeloid leukemia. Leukemia 21:1901–1906
Müller A, Lange K, Gaiser T, Hofmann M, Bartels H, Feller AC, Merz H (2002) expression of angiopoietin-1 and its receptor TEK system in hemopoietic cells from patients with myeloid leukemia. Leuk Res 26163–26168
Amo Y, Masuzawa M, Hamada Y, Katsuoka K (2004) Observations on angiopoietin 2 in patients with angiosarcoma. Sry Dermatol 150:1028–1029
Cine GJ, Blann AD, Stonelake PS, Ryan P, Lip GY (2003) Plasma angiopoietin-1, angiopoietin-2 and Tie-2 in breast and prostate cancer: a comparison with VEGF and FIt-1. Eur J Clin Invest 33:883–890
Oliner J, Min H et al. (2004) Suppression of angiogenesis and tumor growth by selective inhibition of angiopoitin-2. Cancer Cell 6:507–516
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Aref, S., El Menshawy, N., Azmy, E. et al. Soluble angiopoietin-2/sTie2 receptor ratio is an independent prognostic marker in adult acute myeloid leukemia. Indian J Hematol Blood Transfus 25, 17–22 (2009). https://doi.org/10.1007/s12288-009-0004-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12288-009-0004-8