Poster Presentation 25th Lorne Cancer Conference 2013

Potential roles for thrombopoietin and platelets in lymphoma (#222)

Marion Lebois 1 , Ping Cannon 1 , Diane Moujalled 1 , Angelika Rutgersson 1 , Fatme Faraj 1 , Andrew Roberts 1 , Benjamin T Kile 1 , Kylie Mason 1 , Warren S Alexander 1 , Emma C Josefsson 1
  1. Walter and Eliza Hall Institute, Melbourne, VIC, Australia

Platelets are the blood cells that protect us from bleeding to death when we suffer an injury, quickly forming a plug that seals the wound. In contrast to their protective roles, platelets have been linked to promotion of metastasis, and in some cases to supporting the tumor vasculature in solid tumors. However, the role of platelets in blood cancers, such as lymphoma and leukemia, is largely unknown.

We set out to investigate if changes in platelet number and signaling via thrombopoietin, the primary regulator of platelet production, would influence myc driven B-cell lymphoma progression. To test this, Eµ-Myc transgenic mice a well-established model of human Burkitt’s lymphoma, were mated with Mpl-/- mice that have severe reductions in platelets, megakaryocytes and megakaryocyte progenitor cells due to lack of thrombopoietin signaling through Mpl. In addition, we mated Eµ-Myc mice with TpoTg transgenic mice which overexpress thrombopoietin leading to increased megakaryopoiesis and high platelet numbers. As previously described, Mpl-/-mice exhibit platelet counts ~10% of wild type levels. While TpoTgmice have 3.5 times higher platelet counts, compared to wild type mice.

Our preliminary data indicate that changes in platelet number and/or signaling via thrombopoietin influence tumor onset and overall survival in Myc driven lymphoma. Thrombopoietin mimetic drugs were recently approved to treat immune thrombocytopenia and are currently in clinical trials for use in chemotherapy-induced thrombocytopenia. It is therefore important to better understand the roles of thrombopoietin and platelets in cancer, including lymphoma and leukemia.