deoxyguanosine-triphosphate has been researched along with Leukemia--Lymphocytic--Chronic--B-Cell* in 2 studies
1 review(s) available for deoxyguanosine-triphosphate and Leukemia--Lymphocytic--Chronic--B-Cell
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Purine nucleoside phosphorylase inhibition as a novel therapeutic approach for B-cell lymphoid malignancies.
Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of ribonucleosides and 2'-deoxyribonucleosides to their respective bases. Endogenous PNP deficiency leads to specific T-cell immunodeficiency, a genetic disease that has prompted the development of PNP inhibitors as potential therapies for T-cell-mediated diseases. PNP inhibition leads to the elevation of 2'-deoxyguanosine levels and accumulation of intracellular deoxyguanosine 5'-triphosphate, inducing cellular apoptosis. Forodesine is a highly potent, orally active, rationally designed PNP inhibitor that has shown activity in preclinical studies with malignant cells and clinical utility against T-cell acute lymphoblastic leukemia and cutaneous T-cell lymphoma. Additional preliminary findings support its use for the management of some B-cell malignancies. Topics: Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Deoxyguanine Nucleotides; Humans; Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Purine Nucleosides; Purine-Nucleoside Phosphorylase; Pyrimidinones | 2007 |
1 other study(ies) available for deoxyguanosine-triphosphate and Leukemia--Lymphocytic--Chronic--B-Cell
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SAMHD1 Limits the Efficacy of Forodesine in Leukemia by Protecting Cells against the Cytotoxicity of dGTP.
The anti-leukemia agent forodesine causes cytotoxic overload of intracellular deoxyguanosine triphosphate (dGTP) but is efficacious only in a subset of patients. We report that SAMHD1, a phosphohydrolase degrading deoxyribonucleoside triphosphate (dNTP), protects cells against the effects of dNTP imbalances. SAMHD1-deficient cells induce intrinsic apoptosis upon provision of deoxyribonucleosides, particularly deoxyguanosine (dG). Moreover, dG and forodesine act synergistically to kill cells lacking SAMHD1. Using mass cytometry, we find that these compounds kill SAMHD1-deficient malignant cells in patients with chronic lymphocytic leukemia (CLL). Normal cells and CLL cells from patients without SAMHD1 mutation are unaffected. We therefore propose to use forodesine as a precision medicine for leukemia, stratifying patients by SAMHD1 genotype or expression. Topics: Animals; Deoxyguanine Nucleotides; Drug Resistance, Neoplasm; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Mice; Mice, Inbred C57BL; Purine Nucleosides; Pyrimidinones; SAM Domain and HD Domain-Containing Protein 1 | 2020 |