Cytotoxic
nucleoside analogs (NA) are important in the treatment of
hematologic malignancies. The NA in routine clinical use include the
pyrimidine analog
cytosine arabinoside (
ara-c), which is extensively used in the treatment of acute
leukemias, and the
purine analogs,
cladribine and
fludarabine. These drugs have mostly been used in the treatment of low grade
hematological malignancies. NA become therapeutically effective only after phosporylation to the
triphosphate level. The 5'-nucleotidases (5'-NTs) dephosphorylate the monophosphate form of NA and, therefore, may affect the pharmacological activity of these
antimetabolites in the clinic. Several 5'-NTs attached to membranes or present in the cytosol or in mitochondria are present in mammalian cells. cN-II, an
IMP-selective 5'-NT, participates in the regulation of
purine deoxyribonucleotide metabolism. cN-II opposes the action of the salvage
enzymes by dephosphorylating
purine nucleoside mononphosphates to
purine nucleosides. Due to its
phosphotransferase activity, cN-II can also phosphorylate
inosine and 2',3'-dideoxyribonucleosides utilizing
IMP as a
phosphate donor. The observation that cytosolic cN-II is able to phosphorylate
purine nucleosides has initiated studies on its potential participation in the metabolism of
anticancer agents and in the development of cN-II inhibitory substances. In this review, we highlight the current knowledge concerning cN-II activity and regulation of intracellular
deoxyribonucleotide pools and it role in
hematological malignancies.