Ex vivo activity of thalidomide in childhood acute leukemia

Abstract

Thalidomide is a drug with anti-angiogenic, anti-inflammatory, immunomodulatory and anti-cancer properties that were found to inhibit the production of TNF-α in vitro, stimulate reactive oxygen species production, and inhibit VEGFR in acute leukemias. Ex vivo activity of thalidomide as a single agent and in combination with prednisolone or cytarabine in childhood acute leukemias was analyzed. Forty samples of childhood acute lymphoblastic leukemia (ALL) and 13 acute myeloid leukemia (AML) were tested for cytotoxicity by the MTT assay and cell cycle phases by flow cytometry. Control studies were performed on 9 samples of normal lymphocytes and 4 cell lines. A weak anti-leukemic activity of thalidomide against childhood leukemic samples was observed. However, in the presence of thalidomide, cytotoxicity of prednisolone or cytarabine, increased 3.3-fold and 2.7-fold, respectively, in childhood ALL but was not changed in AML. Thalidomide increased apoptosis in lymphoblasts, and modulated cell cycle arrest caused by prednisolone but not cytarabine in childhood acute lymphoblastic leukemia samples. Thalidomide potentiated ex vivo sensitivity of childhood ALL cells to prednisolone and cytarabine, while no sensitization effect was observed in AML cells.

Keywords:

• Thalidomide
• prednisolone
• cytarabine
• sensitization
• acute lymphoblastic leukemia
• acute myeloblastic leukemia