TY - JOUR
T1 - Immunocytochemical detection of deoxycytidine kinase in pediatric malignancies in relation to in vitro cytarabine sensitivity
AU - Hubeek, I.
AU - Peters, G. J.
AU - Broekhuizen, A. J.F.
AU - Talianidis, I.
AU - Schouten Van Meeteren, A. Y.N.
AU - Van Wering, E. R.
AU - Gibson, B.
AU - Creutzig, U.
AU - Kaspers, G. J.L.
PY - 2004
Y1 - 2004
N2 - Deoxycytidine kinase (dCK) is essential for the phosphorylation of cytarabine (ara-C), a deoxycytidine analog active against acute leukemias. Resistance to ara-C has been linked to dCK deficiency. In this study we determined the expression of the dCK protein in pediatric malignancies, using immunocytochemistry and related the expression levels to in vitro ara-C sensitivity (measured with the MTT-assay). dCK expression was high in the AML and retinoblastoma samples, in the ALL samples dCK expression ranged from low to very high. The brain tumor samples expressed low levels of dCK. AML was significantly more sensitive in vitro to ara-C compared to ALL (p = 0.03). Retinoblastoma and brain tumor cells were extremely resistant in vitro, we were unable to detect more than 50% ara-C induced cell kill in the majority of samples. Samples were combined in groups according to dCK expression. Samples with low dCK expression were significantly more resistant to ara-C compared to samples with high dCK expression. In conclusion, dCK expression varies between individual samples and between different types of malignancies and may play a role in resistance to ara-C in particular tumor types.
AB - Deoxycytidine kinase (dCK) is essential for the phosphorylation of cytarabine (ara-C), a deoxycytidine analog active against acute leukemias. Resistance to ara-C has been linked to dCK deficiency. In this study we determined the expression of the dCK protein in pediatric malignancies, using immunocytochemistry and related the expression levels to in vitro ara-C sensitivity (measured with the MTT-assay). dCK expression was high in the AML and retinoblastoma samples, in the ALL samples dCK expression ranged from low to very high. The brain tumor samples expressed low levels of dCK. AML was significantly more sensitive in vitro to ara-C compared to ALL (p = 0.03). Retinoblastoma and brain tumor cells were extremely resistant in vitro, we were unable to detect more than 50% ara-C induced cell kill in the majority of samples. Samples were combined in groups according to dCK expression. Samples with low dCK expression were significantly more resistant to ara-C compared to samples with high dCK expression. In conclusion, dCK expression varies between individual samples and between different types of malignancies and may play a role in resistance to ara-C in particular tumor types.
KW - Deoxycytidine kinase
KW - Immunocytochemistry
KW - Pediatric malignancies
UR - http://www.scopus.com/inward/record.url?scp=10344240923&partnerID=8YFLogxK
U2 - 10.1081/NCN-200027613
DO - 10.1081/NCN-200027613
M3 - Article
C2 - 15571257
AN - SCOPUS:10344240923
SN - 1525-7770
VL - 23
SP - 1351
EP - 1356
JO - Nucleosides, Nucleotides and Nucleic Acids
JF - Nucleosides, Nucleotides and Nucleic Acids
IS - 8-9
ER -