Thalidomide increases in vitro sensitivity of childhood acute lymphoblastic leukemia cells to prednisolone and cytarabine

Abstract.

Introduction:

Thalidomide is a derivative of glutamic acid with anti-angiogenic, anti-inflammatory, immunomodulatory and anti-cancer properties that was found to inhibit the production of tumor necrosis factor α in vitro, stimulate reactive oxygen species production, and inhibit vascular endothelial growth factor receptor in acute leukemias. The purpose of this study was to determine the in vitro activity of thalidomide as a single agent and in combination with prednisolone or cytarabine in childhood acute lymphoblastic leukemia (ALL).

Materials and Methods:

Bone marrow samples of 40 childhood ALL patients, normal lymphocytes of 9 healthy adults, and 3 lymphoid cell lines were evaluated for cytotoxicity of thalidomide (alone and in combination with prednisolone and cytarabine) using the MTT assay. Cell cycle analysis was performed by flow cytometry.

Results:

Thalidomide as a single agent had weak antileukemic activity to the childhood ALL samples. However, in the presence of thalidomide the cytotoxicities of prednisolone and cytarabine were increased 3.3-fold (p<0.001) and 2.7-fold (p=0.002), respectively. Thalidomide increased apoptosis in lymphoblasts and modulated the cell-cycle arrest caused by prednisolone, but not that by cytarabine, in childhood ALL samples.

Conclusions:

Thalidomide increases in vitro the sensitivity of childhood ALL cells to prednisolone and cytarabine.