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Relationship of deoxycytidine kinase and cytoplasmic 5'-nucleotidase to the
chemotherapeutic efficacy of 2-chlorodeoxyadenosine
H Kawasaki, CJ Carrera, LD Piro, A Saven, TJ Kipps and DA Carson
Department of Medicine, University of California San Diego, La Jolla
92093-0663.
The agent 2-chlorodeoxyadenosine (2-CdA) has chemotherapeutic activity in
hairy cell leukemia (HCL) and in refractory chronic lymphocytic leukemia
(CLL). The cytotoxic activity of 2-CdA requires the intracellular
accumulation of 2-CdA nucleotides. Deoxycytidine kinase (dCK) and
cytoplasmic 5'-nucleotidase (5'-NT) are the principal enzymes that
phosphorylate 2-CdA and dephosphorylate 2-CdA 5'-monophosphate,
respectively. The net accumulation of 2-CdA nucleotides may therefore
depend on both dCK and 5'-NT. The purpose of the present experiments was to
determine if there is a relationship between pretreatment levels of dCK and
5'-NT in HCL and in CLL cells, and the clinical outcome of 2- CdA
treatment. As measured by a direct immunoassay for dCK in 25 CLL patients,
and by a 5'-NT activity assay in 23 patients, mean dCK levels were
significantly higher in 2-CdA responders than in nonresponders (P <
.01), whereas mean 5'-NT levels were significantly lower in 2-CdA
responders than in nonresponders (P < .05). Mean dCK levels were higher
in six HCL 2-CdA responders than in one nonresponder, whereas mean 5'- NT
levels were lower in the 2-CdA responders than in the nonresponder. These
results suggest that both dCK and 5'-NT are determinants of 2-CdA
responsiveness.
Volume 81,
Issue 3,
pp. 597-601,
02/01/1993
Copyright © 1993 by The American Society of Hematology
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