BMSEHA15
Published online 14 October 2009
Haematologica, Vol 95, Issue 1, 163-167 doi:10.3324/haematol.2009.006411
Copyright © 2010 by Ferrata Storti Foundation
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Multiple Myeloma

Thymosin β4 has tumor suppressive effects and its decreased expression results in poor prognosis and decreased survival in multiple myeloma

Jo Caers1,2, Dirk Hose3,5, Ine Kuipers1, Tomas Jan Bos1, Els Van Valckenborgh1, Eline Menu1, Elke De Bruyne1, Hartmut Goldschmidt3,5, Ben Van Camp1, Bernard Klein4, Karin Vanderkerken1

1 Laboratory of Hematology and Immunology, Vrije Universiteit Brussel, Myeloma Center Brussels, Brussels, Belgium
2 Department of Hematology, CHU Université de Liège, Campus Sart-Tilman, Liège, Belgium
3 Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany
4 Institut National de la Santé et de la Recherche Médicale U475 and Unit for Cellular Therapy, CHU Montpellier, Montpellier, France
5 Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany

Correspondence: Karin Vanderkerken, Vrije Universiteit Brussel (VUB), Department of Hematology and Immunology, Laarbeeklaan 103, B-1090 Brussels, Belgium. E-mail: karin.vanderkerken{at}vub.ac.be

Thymosin β4 (Tβ4) is a polypeptide involved in cellular proliferation, differentiation, and migration, over-expressed in several tumor entities. We evaluated its expression and function in 298 newly diagnosed multiple myeloma patients and the murine 5TMM model. Mean Tβ4 expression was significantly lower in myeloma cells compared to normal plasma cells (P<0.001). The same observation can be made in the 5TMM-mouse model by qRT-PCR and ELISA. Here, Tβ4 overexpression by lentiviral transduction of 5T33MMvt-cells led to significantly decreased proliferative and migratory capacities and increased sensitivity to apoptosis-induction. Mice injected with Tβ4 over-expressing myeloma cells showed a longer survival compared to mice injected with controls (88,9 vs. 65,9 days, P<0.05). In 209 MM patients treated with high-dose therapy and autologous stem cell transplantation, expression of Tβ4 below the median was associated with a significantly shorter event free survival (37.6 vs. 26.2 months, P<0.05). In conclusion, our results indicate a possible tumor suppressive function of Tβ4.

Key words: thymosin β4, cellular proliferation, multiple myeloma.