In vitro efficacy of forodesine and nelarabine (ara-G) in pediatric leukemia

Irene Homminga, C. Michel Zwaan, Chantal Y. Manz, Cynthia Parker, Shanta Bantia, Willem Korstiaan Smits, Fiona Higginbotham, Rob Pieters, Jules P.P. Meijerink

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

34 Citaten (Scopus)


Forodesine and nelarabine (the pro-drug of ara-G) are 2 nucleoside analogues with promising anti-leukemic activity. To better understand which pediatric patients might benefit from forodesine or nelarabine (ara-G) therapy, we investigated the in vitro sensitivity to these drugs in 96 diagnostic pediatric leukemia patient samples and the mRNA expression levels of different enzymes involved in nucleoside metabolism. Forodesine and ara-G cytotoxicities were higher in T-cell acute lymphoblastic leukemia (T-ALL) samples than in B-cell precursor (BCP)-ALL and acute myeloid leukemia (AML) samples. Resistance to forodesine did not preclude ara-G sensitivity and vice versa, indicating that both drugs rely on different resistance mechanisms. Differences in sensitivity could be partly explained by significantly higher accumulation of intra-cellular dGTP in forodesine-sensitive samples compared with resistant samples, and higher mRNA levels of dGK but not dCK. The mRNA levels of the transporters ENT1 and ENT2 were higher in ara-G-sensitive than -resistant samples. We conclude that especially T-ALL, but also BCP-ALL, pediatric patients may benefit from forodesine or nelarabine (ara-G) treatment.

Originele taal-2Engels
Pagina's (van-tot)2184-2190
Aantal pagina's7
Nummer van het tijdschrift8
StatusGepubliceerd - 25 aug. 2011
Extern gepubliceerdJa


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