Sorm F, Piskala A, Cihak A, Vesely J. 5-Azacytidine, a new, highly effective cancerostatic. Experientia. 1964;20:202–3.
Article
CAS
PubMed
Google Scholar
Jones PA, Taylor SM. Cellular differentiation, cytidine analogs and DNA methylation. Cell. 1980;20:85–93.
Article
CAS
PubMed
Google Scholar
Von Hoff DD, Slavik M, Muggia FM. 5-Azacytidine. A new anticancer drug with effectiveness in acute myelogenous leukemia. Ann Intern Med. 1976;85(2):237–45.
Article
Google Scholar
Jones PA, Taylor SM. Hemimethylated duplex DNAs prepared from 5-azacytidine-treated cells. Nucleic Acids Res. 1981;9:2933–47.
Article
CAS
PubMed
PubMed Central
Google Scholar
Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacytidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002;20:2429–40.
Voso MT, Scardocci A, Guidi F, et al. Aberrant methylation of DAP-kinase in therapy-related acute myeloid leukemia and myelo-dysplastic syndromes. Blood. 2004;103:698–700.
Article
CAS
PubMed
Google Scholar
Lübbert M, Suciu S, Baila L, et al. Low-Dose decitabine Versus Best Supportive Care in Elderly Patients With Intermediate- or High-Risk Myelodysplastic Syndrome (MDS) Ineligible for Intensive Chemotherapy: Final Results of the Randomized Phase III Study of the European Organisation forResearch and Treatment of Cancer Leukemia Group and the German MDS Study Group. J Clin Oncol. 2011;29:1987–96.
Article
PubMed
Google Scholar
Kantarjian H, Oki Y, Garcia-Manero G, et al. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood. 2007;109(1):52–7.
Article
CAS
PubMed
Google Scholar
Rius M, Stresemann C, Keller D, et al. Human concentrative nucleoside transporter 1-mediated uptake of 5-azacytidine enhances DNA demethylation. Mol Cancer Ther. 2009;8:225–31.
Article
CAS
PubMed
Google Scholar
Li LH, Olin EJ, Buskirk HH, Reineke LM. Cytotoxicity and mode of action of 5-azacytidine on L1210 leukemia. Cancer Res. 1970;30(11):2760–9.
CAS
PubMed
Google Scholar
Leonhardt H, Page AW, Weier HU, Bestor TH. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell. 1992;71(5):865–73.
Article
CAS
PubMed
Google Scholar
Liu K, Wang YF, Cantemir C, Muller MT. Endogenous assays of DNA methyltransferases: Evidence for differential activities of DNMT1, DNMT2, and DNMT3 in mammalian cells in vivo. Mol Cell Biol. 2003;23(8):2709–19.
Article
CAS
PubMed
PubMed Central
Google Scholar
Taylor SM, Jones PA. Mechanism of action of eukaryotic DNA methyltransferase. Use of 5-azacytosinecontaining DNA. J Mol Biol. 1982;162(3):679–92.
Article
CAS
PubMed
Google Scholar
Bender CM, Zingg JM, Jones PA. DNA methylation as a target for drug design. Pharm Res. 1998;15(2):175–87.
Article
CAS
PubMed
Google Scholar
Juttermann R, Li E, Jaenisch R. Toxicity of 5-aza-2_-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Proc Natl Acad Sci U S A. 1994;91:11797–801.
Article
CAS
PubMed
PubMed Central
Google Scholar
Palii SS, Van Emburgh BO, Sankpal UT, et al. DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B. Mol Cell Biol. 2008;28(2):752–71.
Article
CAS
PubMed
Google Scholar
Orta ML, Höglund A, Calderón-Montaño JM, et al. The PARP inhibitor Olaparib disrupts base excision repair of 5-aza-2'-deoxycytidine lesions. Nucleic Acids Res. 2014;42(14):9108–20.
Article
PubMed
PubMed Central
Google Scholar
Mortusewicz O, Schermelleh L, Walter J, et al. Recruitment of DNA methyltransferase I to DNA repair sites. Proc Natl Acad Sci U S A. 2005;102(25):8905–9.
Article
CAS
PubMed
PubMed Central
Google Scholar
Vispé S, Deroide A, Davoine E, et al. Consequences of combining siRNA-mediated DNA methyltransferase 1 depletion with 5-aza-2'-deoxycytidine in human leukemic KG1 cells. Oncotarget. 2015;6(17):15265–82.
Article
PubMed
PubMed Central
Google Scholar
Lee TT, Karon MR. Inhibition of protein synthesis in 5-azacytidine-treated HeLa cells. Biochem Pharmacol. 1976;25(15):1737–42.
Article
CAS
PubMed
Google Scholar
Lu LJW, Randerath K. Mechanism of 5-azacytidine-induced transfer RNA cytosine-5-methyltransferase deficiency. Cancer Res. 1980;40(8):2701–5.
CAS
PubMed
Google Scholar
Schaefer M, Hagemann S, Hanna K, Lyko F. Azacytidine inhibits RNA methylation at DNMT2 target sites in human cancer cell lines. Cancer Res. 2009;69:8127–32.
Article
CAS
PubMed
Google Scholar
Aimiuwu J, Wang H, Chen P, et al. RNA-dependent inhibition of ribonucleotide reductase is a major pathway for 5-azacytidine activity in acute myeloid leukemia. Blood. 2012;119(22):5229–38.
Article
CAS
PubMed
PubMed Central
Google Scholar
Chiappinelli KB, Strissel PL, Desrichard A, et al. Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses. Cell. 2015;162(5):974–86.
Article
CAS
PubMed
Google Scholar
Li H, Chiappinelli KB, Guzzetta AA, Easwaran H, et al. Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget. 2014;5:587–98.
Article
PubMed
PubMed Central
Google Scholar
Wrangle J, Wang W, Koch A, et al. Alterations of immune response of non-small cell lung cancer with azacytidine. Oncotarget. 2013;4:2067–79.
Article
PubMed
PubMed Central
Google Scholar
Fabre C, Grosjean J, Tailler M, et al. A novel effect of DNA methyltransferase and histone deacetylase inhibitors: nfkappab inhibition in malignant myeloblasts. Cell Cycle. 2008;7(14):2139–45.
Article
CAS
PubMed
Google Scholar
Costantini B, Kordasti SY, Kulasekararaj AG, et al. 5-azacytidine specifically depletes regulatory t cells (tregs) in myelodysplastic syndrome (mds) patients. ASH Annual, Meeting Abstracts. 2011;118(21):787.
Google Scholar
Cihák A. Biological effects of 5-azacytidine in eukaryotes. Oncology. 1974;30:405–22.
Article
PubMed
Google Scholar
Poirier S, Samami S, Mamarbachi M, et al. The Epigenetic Drug 5-Azacytidine Interferes with Cholesterol and Lipid Metabolism. J Biol Chem. 2014;289(27):18736–51.
Article
CAS
PubMed
PubMed Central
Google Scholar
Vesely J. Mode of action and effects of 5-azacytidine and of its derivatives in eukaryotic cells. Pharmacol Ther. 1985;28:227–35.
Article
CAS
PubMed
Google Scholar
Glover AB, Leyland-Jones B. Biochemistry of azacytidine: a review. Cancer Treat Rep. 1987;71:959–64.
CAS
PubMed
Google Scholar
Chabner BA, Drake JC, Johns DG. Deamination of 5-azacytidine by a human leukemia cell cytidine deaminase. Biochem Pharmacol. 1973;22:2763–5.
Article
CAS
PubMed
Google Scholar
Voso MT, Breccia M, Lunghi M, et al. Rapid loss of response after withdrawal of treatment with azacitidine: a case series in patients with higher-risk myelodysplastic syndromes or chronic myelomonocytic leukemia. Eur J Haematol. 2013;90(4):345–8.
Article
PubMed
Google Scholar
Liu Z, Marcucci G, Byrd JC, et al. Characterization of decomposition products and preclinical and low dose clinical pharmacokinetics of decitabine (5-aza-20-deoxycytidine) by a new liquid chromatography/tandem mass spectrometry quantification method. Rapid Commun Mass Spectrom. 2006;20:1117–26.
Article
CAS
PubMed
Google Scholar
Marcucci G, Silverman L, Eller M, et al. Bioavailabilit of azacitidine subcutaneous versus intravenous in patients with the myelodysplastic syndromes. J Clin Pharmacol. 2005;45:597–602.
Article
CAS
PubMed
Google Scholar
Stresemann C, Bokelmann I, Mahlknecht U, Lyko T. Therapeutics, Targets, and Development: Azacytidine causes complex DNA methylation responses in myeloid leukemia. Mol Cancer Ther September. 2008;7:2998–3005.
Article
CAS
Google Scholar
Yang AS, Doshi KD, Choi SW, et al. DNA methylation changes after 5-aza-20-deoxycytidine therapy in patients with leukemia. Cancer Res. 2006;66:5495–503.
Article
CAS
PubMed
Google Scholar
Adams RL, Fulton J, Kirk D. The effect of 5-azadeoxycytidine on cell growth and DNA methylation. Biochim Biophys Acta. 1982;697:286–94.
Article
CAS
PubMed
Google Scholar
Momparler RL, Momparler LF, Samson J. Comparison of the antileukemic activity of 5-aza-2'-deoxycytidine, 1-ß-D-arabinofuranosyl-cytosine and 5-azacytidine against L1210 leukemia. Leukemia Res. 1984;8:1043–9.
Article
CAS
Google Scholar
Momparler RL, Rossi M, Bouchard J, et al. Kinetic interaction of 5-AZA-2'-deoxycytidine-5'-monophosphate and its 5'-triphosphate with deoxycytidylate deaminase. Mol Pharmacol. 1984;25:436–40.
CAS
PubMed
Google Scholar
Momparler RL, Onetto-Pothier N, Momparler LF. Comparison of antineoplastic activity of cytosine arabinoside and 5-aza-2'-deoxycytidine against human leukemic cells of different phenotype. Leuk Res. 1990;14(9):755–60.
Article
CAS
PubMed
Google Scholar
Covey JM, Zaharko DS. Comparison of the in vitro cytotoxicity (L1210) of 5-aza-2'-deoxycytidine with its therapeutic and toxic effects in mice. Eur J Cancer Clin Oncol. 1985;21:109–17.
Article
CAS
PubMed
Google Scholar
Issa JP, Garcia-Manero G, Giles FJ, et al. Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignancies. Blood. 2004;103(5):1635–40.
Article
CAS
PubMed
Google Scholar
Jabbour E, Cortes JE, Kantarjian HM. Molecular monitoring in chronic myeloidleukemia: response to tyrosine kinase inhibitors and prognostic implications. Cancer. 2008;112(10):2112–8.
Article
CAS
PubMed
Google Scholar
Hollenbach PW, Nguyen AN, Brady H, et al. A comparison of azacitidine and decitabine activities in acute myeloid leukemia cell lines. PLoS One. 2010;5(2):e9001.
Article
PubMed
PubMed Central
Google Scholar
Greenberg PL, Stone RM, Bejar R, et al. Myelodysplastic syndromes, version 2.2015. J Natl Compr Canc Netw. 2015;13(3):261–72.
CAS
PubMed
PubMed Central
Google Scholar
Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacytidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10(3):223–32.
Article
CAS
PubMed
PubMed Central
Google Scholar
Gurion R, Vidal L, Gafter-Gvili A, et al. 5-azacytidine prolongs overall survival in patients with myelodysplastic syndrome - a systematic review and meta-analysis. Haematologica. 2010;95(2):303–10.
Article
CAS
PubMed
Google Scholar
Gore SD, Fenaux P, Santini V, et al. A multivariate analysis of the relationship between response and survival among patients with higher-risk myelodysplastic syndromes treated within azacytidine or conventional care regimens in the randomized AZA-001 trial. Haematologica. 2013;98(7):1067–72.
Article
CAS
PubMed
PubMed Central
Google Scholar
Götze K, Platzbecker U, Giagounidis A, et al. Azacitidine for treatment of patients with myelodysplastic syndromes (MDS): practical recommendations of the German MDS Study Group. Ann Hematol. 2010;89(9):841–50.
Article
PubMed
Google Scholar
Cogle CR, Scott BL, Boyd T, Garcia-Manero G. Oral Azacytidine (CC-486) for the Treatment of Myelodysplastic Syndromes and Acute Myeloid Leukemia. Oncologist. 2015;20(12):1404–12.
Article
PubMed
Google Scholar
Garcia-Manero G, Gore SD, Cogle C, et al. Phase I study of oral azacytidine in myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. J Clin Oncol. 2011;29(18):2521–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Platzbecker U, Wermke M, Radke J, et al. Azacytidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial. Leukemia. 2011;26:381–9.
Article
PubMed
PubMed Central
Google Scholar
Schroeder T, Rachlis E, Bug G, et al. Treatment of acute myeloid leukemia or myelodysplastic syndrome relapse after allogeneic stem cell transplantation with azacytidine and donor lymphocyte infusions - a retrospective multicenter analysis from the German Cooperative Transplant Study Group. Biol Blood Marrow Transplant. 2015;21:653–60.
Article
CAS
PubMed
Google Scholar
Steensma DP, Baer MR, Slack JL, et al. Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. J Clin Oncol. 2009;27(23):3842–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Fenaux P, Mufti GJ, Hellström-Lindberg E, et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010;28(4):562–9.
Article
CAS
PubMed
Google Scholar
Pleyer L, Burgstaller S, Girschikofsky M, et al. Azacytidine in 302 patients with WHO-defined acute myeloid leukemia: results from the Austrian Azacytidine Registry of the AGMT-Study Group. Ann Hematol. 2014;93(11):1825–38.
Article
CAS
PubMed
PubMed Central
Google Scholar
Thépot S, Itzykson R, Seegers V, Groupe Francophone des Myélodysplasies (GFM), Acute Leukemia French Association (ALFA); Groupe Ouest-Est des Leucémies Aiguës, Groupe Francophone des Myélodysplasies (GFM), Acute Leukemia French Association (ALFA); Groupe Ouest-Est des Leucémies Aiguës; Maladies du Sang (GOELAMS). Azacitidine in untreated acute myeloid leukemia: a report on 149 patients. Am J Hematol. 2014;89(4):410–6.
Article
PubMed
Google Scholar
Dombret H, Seymour JF, Butrym A, et al. International phase 3 study of azacytidine vs conventional care regimens in older patients with newly diagnosed AML with >30 % blasts. Blood. 2015;126:291–9.
Article
CAS
PubMed
PubMed Central
Google Scholar
Müller-Tidow C, Tschanter P, Röllig C, et al. Azacytidine in combination with intensive induction chemotherapy in older patients with acute myeloid leukemia: The AML-AZA trial of the study alliance leukemia. Leukemia. 2016;30(3):555–61.
Article
PubMed
Google Scholar
Kantarjian H, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30:2670–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lee YG, Kim I, Yoon SS, et al. Comparative analysis between azacitidine and decitabine for the treatment of myelodysplastic syndromes. Br J Haematol. 2013;161(3):339–47.
Article
CAS
PubMed
Google Scholar
Bejar R, Stevenson K, Abdel-Wahab O, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364(26):2496–506.
Article
CAS
PubMed
PubMed Central
Google Scholar
Haferlach T, Nagata Y, Grossmann V, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia. 2014;28(2):241–7.
Article
CAS
PubMed
Google Scholar
Papaemmanuil E, Gerstung M, Malcovati L, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122(22):3616–27.
Article
CAS
PubMed
PubMed Central
Google Scholar
Fandy TE, Herman JG, Kerns P, et al. Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies. Blood. 2009;114(13):2764–73.
Article
CAS
PubMed
PubMed Central
Google Scholar
Qin T, Castoro R, El Ahdab S, et al. Mechanisms of resistance to decitabine in the myelodysplastic syndrome. PLoS One. 2011;6(8):e23372.
Article
CAS
PubMed
PubMed Central
Google Scholar
Valencia A, Masala E, Rossi A, et al. Expression of nucleoside-metabolizing enzymes in myelodysplastic syndromes and modulation of response to azacytidine. Leukemia. 2014;28(3):621–8.
Article
CAS
PubMed
Google Scholar
Bejar R, Lord A, Stevenson K, et al. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood. 2014;124(17):2705–12.
Article
CAS
PubMed
PubMed Central
Google Scholar
Itzykson R, Kosmider O, Cluzeau T, et al. Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leukemia. 2011;25(7):1147–52.
Article
CAS
PubMed
Google Scholar
Traina F, Visconte V, Elson P, et al. Impact of molecular mutations on treatment response to DNMT inhibitors in myelodysplasia and related neoplasms. Leukemia. 2014;28(1):78–87.
Article
CAS
PubMed
Google Scholar
Cluzeau T, Robert G, Mounier N, et al. BCL2L10 is a predictive factor for resistance to azacytidine in MDS and AML patients. Oncotarget. 2012;3:490–501.
Article
PubMed
PubMed Central
Google Scholar
Müller-Thomas C, Rudelius M, Rondak I-C, et al. Response to azacytidine is independent of p53 expression in higher-risk myelodysplastic syndromes and secondary acute myeloid leukemia. Haematologica. 2014;2:179–81.
Article
Google Scholar
Meldi K, Qin T, Buchi F, et al. Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia. J Clin Invest. 2015;125(5):1857–72.
Article
PubMed
PubMed Central
Google Scholar
Craddock C, Quek L, Goardon N, et al. Azacytidine fails to eradicate leukemic stem/progenitor cell populations in patients with acute myeloid leukemia and myelodysplasia. Leukemia. 2013;27(5):1028–36.
Article
CAS
PubMed
Google Scholar
Merlevede J, Droin N, Qin T, et al. Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents. Nat Commun. 2016;7:10767.
Article
CAS
PubMed
PubMed Central
Google Scholar
Prebet T, Gore SD, Esterni B, et al. Outcome of High-Risk Myelodysplastic Syndrome After Azacytidine Treatment Failure. J Clin Oncol. 2011;29(24):3322–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Borthakur G, Ahdab SE, Ravandi F, et al. Activity of decitabine in patients with myelodysplastic syndrome previously treated with azacytidine. Leuk Lymphoma. 2008;49(4):690–5.
Article
CAS
PubMed
PubMed Central
Google Scholar
Cameron EE, Bachman KE, Myohanen S, et al. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet. 1999;21:103–7.
Article
CAS
PubMed
Google Scholar
Navada SC, Steinmann J, Lübbert M, Silverman LR. Clinical development of demethylating agents in hematology. J Clin Invest. 2014;124(1):40–6.
Article
CAS
PubMed
PubMed Central
Google Scholar
Sekeres MA, Tiu RV, Komrokji R, et al. Phase 2 study of the lenalidomide and azacytidine combination in patients with higher-risk myelodysplastic syndromes. Blood. 2012;120(25):4945–51.
Article
CAS
PubMed
PubMed Central
Google Scholar
Daver N, Kantarjian H, Ravandi F, et al. A phase II study of decitabine and gemtuzumab ozogamicin in newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndrome. Leukemia. 2016;30(2):268–73.
Article
CAS
PubMed
Google Scholar
Nuthalapati S, Zhou Q, Guo P, et al. Preclinical pharmacokinetic and pharmacodynamic evaluation of novel anticancer agents, ON01910.Na (Rigosertib, Estybon™) and ON013105, for brain tumor chemotherapy. Pharm Res. 2012;29(9):2499–511.
Article
CAS
PubMed
Google Scholar
Gangat N, Patnaik MM, Tefferi A. Myelodysplastic syndromes: Contemporary review and how we treat. Am J Hematol. 2016;91(1):76–89.
Article
CAS
PubMed
Google Scholar
Fan H, Lu X, Wang X, Liu Y, Guo B, et al. Low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors: a phase I/II report. J Immunol Res. 2014;2014:371087.
PubMed
PubMed Central
Google Scholar
Juergens RA, Wrangle J, Vendetti FP, et al. Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer. Cancer Discov. 2011;1(7):598–607.
Article
CAS
PubMed
PubMed Central
Google Scholar
Nervi C, De Marinis E, Codacci-Pisanelli G. Epigenetic treatment of solid tumours: a review of clinical trials. Clin Epigenetics. 2015;7:127.
Article
PubMed
PubMed Central
Google Scholar