Figure 1 | British Journal of Cancer

Figure 1

From: The human equilibrative nucleoside transporter 1 mediates in vitro cytarabine sensitivity in childhood acute myeloid leukaemia

Figure 1

Metabolism of ara-C. Ara-C enters the cell via the equilibrative nucleoside transporter 1 (hENT1; 1). Inside the cell, ara-C is phosphorylated to ara-CMP by deoxycytidine kinase (dCK; 2). Ara-CMP is subsequently phosphorylated to ara-CTP, the active metabolite. Incorporation of ara-CTP into the DNA blocks DNA synthesis and leads to cell death. Ara-CTP formation can be obstructed. Pyrimidine nucleotidase I (PN-I; 3) opposes the action of dCK. Cytidine deaminase (CDA; 4) and deoxycytidylate deaminase (dCMPD; 5) convert ara-C to ara-U, and ara-CMP to ara-UMP, respectively. Increased intracellular dCTP pools antagonise the formation of ara-CTP. dCTP can be synthesised directly via the de novo pathway by ribonucleotide reductase (6). CTP synthetase (CTPs; 7) converts uridine triphosphate to CTP. Because aberrant expression of these enzymes may be related to in vitro sensitivity to ara-C, and other deoxynucleoside analogues, we determined the mRNA expression of the target genes in AML.

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