Helv. Chim. Acta 2019, 102, e1800229
[7] L. H. Li, E. J. Olin, H. H. Buskirk, L. M. Reineke, ‘Cytotoxicity
count acute myeloid leukemias’, Leukemia 2011, 25, 1147–
1152.
and mode of action of 5-azacytidine on L1210 leukemia’,
Cancer Res. 1970, 30, 2760–2769.
[21] R. Itzykson, O. Kosmider, A. Renneville, V. Gelsi-Boyer, M.
Meggendorfer, M. Morabito, C. Berthon, L. Adès, P. Fenaux,
O. Beyne-Rauzy, N. Vey, T. Braun, T. Haferlach, F. Dreyfus,
N. C. P. Cross, C. Preudhomme, O. A. Bernard, M. Fontenay,
W. Vainchenker, S. Schnittger, D. Birnbaum, N. Droin, E.
Solary, ‘Prognostic Score Including Gene Mutations in
Chronic Myelomonocytic Leukemia’, J. Clin. Oncol. 2013,
31, 2428–2436.
[22] R. Bejar, A. Lord, K. Stevenson, M. Bar-Natan, A. Pérez-
Ladaga, J. Zaneveld, H. Wang, B. Caughey, P. Stojanov, G.
Getz, G. Garcia-Manero, H. Kantarjian, R. Chen, R. M. Stone,
D. Neuberg, D. P. Steensma, B. L. Ebert, ‘TET2 mutations
predict response to hypomethylating agents in myelodys-
plastic syndrome patients’, Blood 2014, 124, 2705–2712.
[23] M. Xie, Q. Jiang, Y. Xie, ‘Comparison Between Decitabine
and Azacitidine for the Treatment of Myelodysplastic
Syndrome: A Meta-Analysis With 1392 Participants’, Clin.
Lymphoma Myeloma Leuk. 2015, 15, 22–28.
[8] E. Flatau, F. A. Gonzales, L. A. Michalowsky, P. A. Jones,
‘DNA methylation in 5-aza-2’-deoxycytidine-resistant var-
iants of C3H 10T1/2 C18 cells’, Mol. Cell. Biol. 1984, 4,
2098–2102.
[9] J. K. Christman, ‘5-Azacytidine and 5-aza-2’-deoxycytidine
as inhibitors of DNA methylation: mechanistic studies and
their implications for cancer therapy’, Oncogene 2002, 21,
5483–5495.
[10] R. Jüttermann, E. Li, R. Jaenisch, ‘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. USA 1994, 91,
11797–11801.
[11] D. Kuch, L. Schermelleh, S. Manetto, H. Leonhardt, T. Carell,
‘Synthesis of DNA Dumbbell Based Inhibitors for the
Human DNA Methyltransferase Dnmt1’, Angew. Chem. Int.
Ed. 2008, 47, 1515–1518.
[12] L. Schermelleh, F. Spada, H. P. Easwaran, K. Zolghadr, J. B.
Margot, M. C. Cardoso, H. Leonhardt, ‘Trapped in action:
direct visualization of DNA methyltransferase activity in
living cells’, Nat. Methods 2005, 2, 751–756.
[13] P. A. Jones, S. M. Taylor, ‘Cellular differentiation, cytidine
analogs and DNA methylation’, Cell 1980, 20, 85–93.
[14] M. Daskalakis, T. T. Nguyen, C. Nguyen, P. Guldberg, G.
Köhler, P. Wijermans, P. A. Jones, M. Lübbert, ‘Demethyla-
tion of a hypermethylated P15/INK4B gene in patients with
myelodysplastic syndrome by 5-Aza-2’-deoxycytidine (dec-
itabine) treatment’, Blood 2002, 100, 2957–2964.
[15] M. S. Soengas, P. Capodieci, D. Polsky, J. Mora, M. Esteller,
X. Opitz-Araya, R. McCombie, J. G. Herman, W. L. Gerald,
Y. A. Lazebnik, C. Cordón-Cardó, S. W. Lowe, ‘Inactivation of
the apoptosis effector Apaf-1 in malignant melanoma’,
Nature 2001, 409, 207–211.
[16] M. G. Goll, F. Kirpekar, K. A. Maggert, J. A. Yoder, C.-L. Hsieh,
X. Zhang, K. G. Golic, S. E. Jacobsen, T. H. Bestor, ‘Methyl-
ation of tRNAAsp by the DNA Methyltransferase Homolog
Dnmt2’, Science 2006, 311, 395–398.
[17] S. Hussain, A. A. Sajini, S. Blanco, S. Dietmann, P. Lombard,
Y. Sugimoto, M. Paramor, J. G. Gleeson, D. T. Odom, J. Ule,
M. Frye, ‘NSun2-Mediated Cytosine-5 Methylation of Vault
Noncoding RNA Determines Its Processing into Regulatory
Small RNAs’, Cell Rep. 2013, 4, 255–261.
[18] Y. Cámara, J. Asin-Cayuela, C. B. Park, M. D. Metodiev, Y.
Shi, B. Ruzzenente, C. Kukat, B. Habermann, R. Wibom, K.
Hultenby, T. Franz, H. Erdjument-Bromage, P. Tempst, B. M.
Hallberg, C. M. Gustafsson, N. G. Larsson, ‘MTERF4 Regu-
lates Translation by Targeting the Methyltransferase
NSUN4 to the Mammalian Mitochondrial Ribosome’, Cell
Metab. 2011, 13, 527–539.
[19] S. Haag, A. S. Warda, J. Kretschmer, M. A. Günnigmann, C.
Höbartner, M. T. Bohnsack, ‘NSUN6 is a human RNA
methyltransferase that catalyzes formation of m5C72 in
specific tRNAs’, RNA 2015, 21, 1532–1543.
[20] R. Itzykson, O. Kosmider, T. Cluzeau, V. Mansat-De Mas, F.
Dreyfus, O. Beyne-Rauzy, B. Quesnel, N. Vey, V. Gelsi-Boyer,
S. Raynaud, C. Preudhomme, L. Adès, P. Fenaux, M.
Fontenay, ‘Impact of TET2 mutations on response rate to
azacitidine in myelodysplastic syndromes and low blast
[24] K.-T. Lin, R. L. Momparlerm, G. E. Rivard, ‘High-performance
Liquid Chromatographic Analysis of Chemical Stability of
5-aza-2’-Deoxycytidine’, J. Pharm. Sci. 1981, 70, 1228–
1232.
[25] D. K. Rogstad, J. L. Herring, J. A. Theruvathu, A. Burdzy, C. C.
Perry, J. W. Neidigh, L. C. Sowers, ‘Chemical Decomposition
of 5-aza-2’-deoxycytidine (Decitabine): Kinetic Analyses
and Identification of Products by NMR, HPLC, and Mass
Spectrometry’, Chem. Res. Toxicol. 2009, 22, 1194–1204.
[26] S. Öz, G. Raddatz, M. Rius, N. Blagitko-Dorfs, M. Lübbert, C.
Maercker, F. Lyko, ‘Quantitative determination of decita-
bine incorporation into DNA and its effect on mutation
rates in human cancer cells’, Nucleic Acids Res. 2014, 42,
e152.
[27] T. Qin, J. Jelinek, J. Si, J. Shu, J.-P. Issa, ‘Mechanisms of
resistance to 5-aza-2’-deoxycytidine in human cancer cell
lines’, Blood 2009, 113, 659–667.
[28] N. M. Anders, J. Liu, T. Wanjiku, H. Giovinazzo, J. Zhou, A.
Vaghasia, W. G. Nelson, S. Yegnasubramanian, M. A. Rudek,
‘Simultaneous quantitative determination of 5-aza-2’-deox-
ycytidine genomic incorporation and DNA demethylation
by liquid chromatography tandem mass spectrometry as
exposure-response measures of nucleoside analog DNA
methyltransferase inhibitors’, J. Chromatogr. B 2016, 1022,
38–45.
[29] M. Matoušová, I. Votruba, M. Otmar, E. Tloušťová, J.
Günterová, H. Mertlíková-Kaiserová, ‘2’-deoxy-5,6-dihydro-
5-azacytidine – a less toxic alternative of 2’-deoxy-5-
azacytidine: a comparative study of hypomethylating
potential’, Epigenetics 2011, 6, 769–776.
[30] J. A. Beisler, M. M. Abbasi, J. A. Kelley, J. S. Driscoll, ‘Syn-
thesis and antitumor activity of dihydro-5-azacytidine, a
hydrolytically stable analogue of 5-azacytidine’, J. Med.
Chem. 1977, 20, 806–812.
[31] A. Unnikrishnan, A. N. Q. Vo, R. Pickford, M. J. Raftery, A. C.
Nunez, A. Verma, L. B. Hesson, J. E. Pimanda, ‘AZA-MS: a
novel multiparameter mass spectrometry method to
determine the intracellular dynamics of azacitidine therapy
In Vivo’, Leukemia 2018, 32, 900–910.
(10 of 11) e1800229
© 2019 Wiley-VHCA AG, Zurich, Switzerland