Absence of mutations in the deoxycytidine kinase (dCK) gene in patients with relapsed and/or refractory acute myeloid leukemia (AML) [1]

TO THE EDITOR
Resistance to chemotherapy is a major problem in the treatment of acute myeloid leukemia (AML). As cytosine-arabinoside (Ara-C) is an important agent in the treatment of AML it is conceivable that leukemic blasts become resistant to Ara-C during the development to relapse/resistant disease. Ara-C is a cytotoxic nucleoside analogue which is phosphorylated intracellularly into its active form Ara-CTP, by the action of three enzymes: deoxycytidine kinase (dCK), deoxycytidine monophosphate (dCMP) kinase and nucleoside diphosphate (NDP) kinase. Ara-CTP inhibits DNA polymerase, and acts by competing with its physiological counterpart, the natural substrate dCTP, for incorporation into nucleic acids. Although several resistance mechanisms are involved in Ara-C metabolism, deoxycytidine kinase (dCK) is of particular interest because it is the rate-limiting enzyme in the phosphorylation process from Ara-C to Ara-CTP. Structural analysis of the dCK gene has revealed mutations which are associated with dCK deficiency and Ara-C resistance in vitro and in vivo. [...]