PNP inhibitors selectively kill cancer cells lacking SAMHD1
Tamara Davenne, Jan Rehwinkel
Abstract
Purine nucleoside phosphorylase inhibitors (PNP-Is) were developed to ablate transformed lymphocytes. However, only some patients with leukemia benefit from PNP-Is. We provide a molecular explanation: the deoxyribonucleoside triphosphate (dNTP) hydrolase SAM and HD domain-containing protein 1 (SAMHD1) prevents the accumulation of toxic dNTP levels during purine nucleoside phosphorylase inhibition. We propose PNP-Is for targeted therapy of patients with acquired SAMHD1 mutations.
Topics & Concepts
Purine nucleoside phosphorylaseSAMHD1NucleosideChronic lymphocytic leukemiaBiologyNucleoside analogueCancer researchLeukemiaPurine analoguePurineChemistryHydrolaseEnzymeBiochemistryGeneticsRNAGeneReverse transcriptaseBiochemical and Molecular ResearchChronic Lymphocytic Leukemia ResearchCytomegalovirus and herpesvirus research