Multiple Myeloma |
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.