Published online 20 February 2008
Haematologica, Vol 93, Issue 3, 451-454 doi:10.3324/haematol.11852
Copyright © 2008 by Ferrata Storti Foundation
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Multiple Myeloma

Normalization of the serum angiopoietin-1 to angiopoietin-2 ratio reflects response in refractory/resistant multiple myeloma patients treated with bortezomib

Konstantinos Anargyrou1,2, Evangelos Terpos1,3, Theodoros P. Vassilakopoulos2, Anastasia Pouli4, Sotirios Sachanas2, Tatiana Tzenou2, Stavroula Masouridis2, Dimitrios Christoulas1,3, Maria K. Angelopoulou2, Evangelia M. Dimitriadou2, Christina Kalpadakis2, Konstantinos Tsionos1, Panayiotis Panayiotidis2, Meletios A. Dimopoulos5, Gerassimos A. Pangalis2,, Marie-Christine Kyrtsonis2 on behalf of the Greek Myeloma Study Group

1 Department of Haematology, 251 General Air Force Hospital, Athens
2 Department of Haematology, National and Kapodistrian University of Athens’ School of Medicine, Athens
3 Department of Medical Research, 251 General Air Force Hospital, Athens
4 Department of Haematology, Saint Savvas Anticancer Hospital, Athens and
5 Department of Clinical Therapeutics, National and Kapodistrian University School of Medicine, Athens, Greece

Correspondence: Gerassimos A. Pangalis, First Department of Internal Medicine and Department of Haematology, National and Kapodistrian University of Athens’ School of Medicine, Laikon University Hospital, Agiou Thoma 17, Athens 11727, Greece. E-mail: pangalis{at}med.uoa.gr; Marie-Christine Kyrtsonis, First Department of Propedeutic Internal Medicine, National and Kapodistrian University of Athens’ School of Medicine, Laikon University Hospital, Agiou Thoma 17, Athens 11727, Greece. Phone: +30-210-7456261. Fax: +30-210-7788830. E-mail: mck{at}ath.forthnet.gr

Neoangiogenesis is involved in the pathophysiology of multiple myeloma and angiopoietins possibly contribute to myeloma-induced neovascularization. Bortezomib’s antineoplastic potential includes an anti-angiogenic effect. We determined serum levels of angiopoietin-1 and angiopoietin-2 with ELISA pre- and post-bortezomib administration in 35 patients with relapsed/refractory multiple myeloma. Pre-bortezomib, serum angiopoietin-1 levels did not differ in patients and in healthy individuals, while serum angiopoietin-2 levels were elevated. Corresponding serum angiopoietin-1/angiopoietin-2 ratio was reduced in patients compared with controls. After treatment, serum angiopoietin-1 levels increased, while serum angiopoietin-2 levels decreased, therefore the angiopoietin-1/angiopoietin-2 ratio increased and normalized. This increase was significant in patients who responded to treatment. In conclusion, angiopoietin-1/angiopoietin-2 ratio normalization reflected response to bortezomib.

Key words: serum angiopoietins, serum Ang-1, Ang-2 ratio, myeloma, bortezomib.