Thalidomide increases in vitro sensitivity of childhood acute lymphoblastic leukemia cells to prednisolone and cytarabine.
BACKGROUND
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 alpha 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).


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.
Czyzewski
Krzysztof
K
Department of Pediatric Hematology and Oncology, Ludwik Rydygier Collegium Medicum of Bydgoszcz, Nicolaus Copernicus University, Bydgoszcz, Poland.
Zaborowska
Agnieszka
A
Styczyński
Jan
J
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007223:Infant; D019169:Jurkat Cells; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011239:Prednisolone / Q000008:administration & dosage; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects
D003561:Cytarabine; D013792:Thalidomide; D011239:Prednisolone