{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:05:50Z","timestamp":1791255950081,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T00:00:00Z","timestamp":1748131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Slovak Agency for Research and Development","award":["APVV-19-0093"],"award-info":[{"award-number":["APVV-19-0093"]}]},{"name":"Slovak Agency for Research and Development","award":["APVV-19-0094"],"award-info":[{"award-number":["APVV-19-0094"]}]},{"name":"Slovak Agency for Research and Development","award":["VEGA 2\/0016\/22"],"award-info":[{"award-number":["VEGA 2\/0016\/22"]}]},{"name":"Grant Agency of the Ministry of Education of the Slovak Republic and the Slovak Academy of Sciences","award":["APVV-19-0093"],"award-info":[{"award-number":["APVV-19-0093"]}]},{"name":"Grant Agency of the Ministry of Education of the Slovak Republic and the Slovak Academy of Sciences","award":["APVV-19-0094"],"award-info":[{"award-number":["APVV-19-0094"]}]},{"name":"Grant Agency of the Ministry of Education of the Slovak Republic and the Slovak Academy of Sciences","award":["VEGA 2\/0016\/22"],"award-info":[{"award-number":["VEGA 2\/0016\/22"]}]},{"name":"the MVTS COST CA21154 project","award":["APVV-19-0093"],"award-info":[{"award-number":["APVV-19-0093"]}]},{"name":"the MVTS COST CA21154 project","award":["APVV-19-0094"],"award-info":[{"award-number":["APVV-19-0094"]}]},{"name":"the MVTS COST CA21154 project","award":["VEGA 2\/0016\/22"],"award-info":[{"award-number":["VEGA 2\/0016\/22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The backbone of therapy for elderly patients with myelodysplastic syndromes and acute myeloid leukemia consists of hypomethylating agents 5-aza-2\u2019-deoxycytidine (DAC) and 5-azacytidine (AZA). However, resistance frequently emerges during treatment. To investigate the mechanisms of resistance, we generated DAC-resistant variants of the acute myeloid leukemia cell lines, MOLM-13 and SKM-1, through their prolonged cultivation in increasing concentrations of DAC. The resistant cell variants, MOLM-13\/DAC and SKM-1\/DAC, exhibited cross-resistance to cytarabine and gemcitabine, but remained sensitive to AZA. Existing studies have suggested that the loss of deoxycytidine kinase (DCK) may play an important role in DAC resistance. DCK is critical for DAC activation, but the precise mechanisms of its downregulation remain incompletely understood. We identified a novel point mutation (A180P) in DCK, which results in acquired DAC resistance. Although the DCK mRNA was actively transcribed, the mutant protein was not detected in DAC-resistant cells. The transfection of HEK293 cells with the mutant DCK, combined with proteasomal inhibition, revealed rapid proteasomal degradation, establishing a mechanistic link between the A180P mutation and DCK loss, not previously described. This highlights the importance of also evaluating DCK at the protein and\/or enzymatic activity levels in patients. The loss of functional DCK impairs the phosphorylation of deoxynucleosides, conferring resistance to DAC, gemcitabine, and cytarabine, but AZA, phosphorylated by uridine\u2013cytidine kinase, remains effective and may represent a therapeutic alternative for patients with acquired DAC resistance.<\/jats:p>","DOI":"10.3390\/ijms26115083","type":"journal-article","created":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T20:26:50Z","timestamp":1748204810000},"page":"5083","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Acquired Resistance to Decitabine Associated with the Deoxycytidine Kinase A180P Mutation: Implications for the Order of Hypomethylating Agents in Myeloid Malignancies Treatment"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4318-1080","authenticated-orcid":false,"given":"Kristina","family":"Simonicova","sequence":"first","affiliation":[{"name":"Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 840 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubos","family":"Janotka","sequence":"additional","affiliation":[{"name":"Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 840 05 Bratislava, Slovakia"},{"name":"Department of Biology, Faculty of Medicine and Dentistry, Palack\u00fd University Olomouc, Hnevotinska 3, 77515 Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Kavcova","sequence":"additional","affiliation":[{"name":"Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 840 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8090-387X","authenticated-orcid":false,"given":"Ivana","family":"Borovska","sequence":"additional","affiliation":[{"name":"Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 840 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7603-4491","authenticated-orcid":false,"given":"Zdena","family":"Sulova","sequence":"additional","affiliation":[{"name":"Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 840 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2174-786X","authenticated-orcid":false,"given":"Albert","family":"Breier","sequence":"additional","affiliation":[{"name":"Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 840 05 Bratislava, Slovakia"},{"name":"Institute of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinsk\u00e9ho 9, 812 37 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7966-5560","authenticated-orcid":false,"given":"Lucia","family":"Messingerova","sequence":"additional","affiliation":[{"name":"Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 840 05 Bratislava, Slovakia"},{"name":"Institute of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinsk\u00e9ho 9, 812 37 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","article-title":"The 5th Edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic\/Dendritic Neoplasms","volume":"36","author":"Khoury","year":"2022","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Fleischmann, M., Schnetzke, U., Hochhaus, A., and Scholl, S. (2021). Management of Acute Myeloid Leukemia: Current Treatment Options and Future Perspectives. Cancers, 13.","DOI":"10.3390\/cancers13225722"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Marques, F.K., and Sabino, A.d.P. (2022). Myelodysplastic Neoplasms: An Overview on Diagnosis, Risk-Stratification, Molecular Pathogenesis, and Treatment. Biomed. Pharmacother., 156.","DOI":"10.1016\/j.biopha.2022.113905"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3109\/03602532.2014.995379","article-title":"Digging Deep into \u201cDirty\u201d Drugs-Modulation of the Methylation Machinery","volume":"47","author":"Pleyer","year":"2015","journal-title":"Drug Metab. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1182\/blood.2022016867","article-title":"Diagnosis and Management of AML in Adults: 2022 Recommendations from an International Expert Panel on Behalf of the ELN","volume":"140","author":"Wei","year":"2022","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.annonc.2020.11.002","article-title":"Myelodysplastic Syndromes: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up\u2020\u2606","volume":"32","author":"Fenaux","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5163","DOI":"10.2217\/fon-2021-0936","article-title":"Real-World Use and Outcomes of Hypomethylating Agent Therapy in Higher-Risk Myelodysplastic Syndromes: Why Are We Not Achieving the Promise of Clinical Trials?","volume":"17","author":"Zeidan","year":"2021","journal-title":"Futur. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100805","DOI":"10.1016\/j.drup.2022.100805","article-title":"Different Mechanisms of Drug Resistance to Hypomethylating Agents in the Treatment of Myelodysplastic Syndromes and Acute Myeloid Leukemia","volume":"61","author":"Janotka","year":"2022","journal-title":"Drug Resist. Updat."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1002\/ajh.26984","article-title":"Myelodysplastic Syndromes: 2023 Update on Diagnosis, Risk-Stratification, and Management","volume":"98","year":"2023","journal-title":"Am. J. Hematol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"\u0160imoni\u010dov\u00e1, K., Janotka, L., Kavcova, H., Sulova, Z., Messingerova, L., and Breier, A. (2023). Resistance of Leukemia Cells to 5-Azacytidine: Different Responses to the Same Induction Protocol. Cancers, 15.","DOI":"10.3390\/cancers15113063"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Janotka, \u013d., Messingerov\u00e1, L., \u0160imoni\u010dov\u00e1, K., Kavcov\u00e1, H., Elefantov\u00e1, K., Sulov\u00e1, Z., and Breier, A. (2021). Changes in Apoptotic Pathways in MOLM-13 Cell Lines after Induction of Resistance to Hypomethylating Agents. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22042076"},{"key":"ref_12","first-page":"2989","article-title":"DNA Methyltransferase Inhibitors and Their Emerging Role in Epigenetic Therapy of Cancer","volume":"33","author":"Gnyszka","year":"2013","journal-title":"Anticancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-023-32509-4","article-title":"DNA Damage, Demethylation and Anticancer Activity of DNA Methyltransferase (DNMT) Inhibitors","volume":"13","author":"Laranjeira","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3324\/haematol.2019.238857","article-title":"Hypo, Hyper, or Combo: New Paradigm for Treatment of Acute Myeloid Leukemia in Older People","volume":"105","author":"Juliusson","year":"2020","journal-title":"Haematologica"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sabini, E., Ort, S., Monnerjahn, C., Konrad, M., and Lavie, A. (2025, March 14). Structure of Human DCK Complexed with 2\u2019-Deoxycytidine and ADP, P 43 21 2 Space Group; 2003. Available online: https:\/\/www.rcsb.org\/pages\/policies.","DOI":"10.2210\/pdb1p61\/pdb"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nsb942","article-title":"Structure of Human DCK Suggests Strategies to Improve Anticancer and Antiviral Therapy","volume":"10","author":"Sabini","year":"2003","journal-title":"Nat. Struct. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"W446","DOI":"10.1093\/nar\/gkab266","article-title":"MutationTaster2021","volume":"49","author":"Steinhaus","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A Method and Server for Predicting Damaging Missense Mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1002\/humu.21047","article-title":"Functional Annotations Improve the Predictive Score of Human Disease-Related Mutations in Proteins","volume":"30","author":"Calabrese","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"W452","DOI":"10.1093\/nar\/gks539","article-title":"SIFT Web Server: Predicting Effects of Amino Acid Substitutions on Proteins","volume":"40","author":"Sim","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.bcp.2014.03.008","article-title":"Constitutive Activation of the ATM\/BRCA1 Pathway Prevents DNA Damage-Induced Apoptosis in 5-Azacytidine-Resistant Cell Lines","volume":"89","author":"Imanishi","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e00206","DOI":"10.1002\/prp2.206","article-title":"Lack of Cross-Resistance to FF-10501, an Inhibitor of Inosine-5\u2032-Monophosphate Dehydrogenase, in Azacitidine-Resistant Cell Lines Selected from SKM-1 and MOLM-13 Leukemia Cell Lines","volume":"4","author":"Murase","year":"2016","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11748","DOI":"10.18632\/oncotarget.14342","article-title":"Establishment and Characterization of Hypomethylating Agent Resistant Cell Lines, MOLM\/AZA-1 and MOLM\/DEC-5","volume":"8","author":"Hur","year":"2017","journal-title":"Oncotarget"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3475","DOI":"10.1038\/s41467-019-11413-4","article-title":"Selective Inactivation of Hypomethylating Agents by SAMHD1 Provides a Rationale for Therapeutic Stratification in AML","volume":"10","author":"Oellerich","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_25","first-page":"1184","article-title":"Adult T-cell Leukemia-lymphoma Acquires Resistance to DNA Demethylating Agents through Dysregulation of Enzymes Involved in Pyrimidine Metabolism","volume":"150","author":"Watanabe","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1182\/blood-2008-02-140038","article-title":"Mechanisms of Resistance to 5-Aza-2\u2019-Deoxycytidine in Human Cancer Cell Lines","volume":"113","author":"Qin","year":"2009","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"761","DOI":"10.3892\/ol.2015.3253","article-title":"Acquired Resistance to Decitabine and Cross-Resistance to Gemcitabine during the Long-Term Treatment of Human HCT116 Colorectal Cancer Cells with Decitabine","volume":"10","author":"Hosokawa","year":"2015","journal-title":"Oncol. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3322","DOI":"10.1200\/JCO.2011.35.8135","article-title":"Outcome of High-Risk Myelodysplastic Syndrome after Azacitidine Treatment Failure","volume":"29","author":"Gore","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.clml.2016.10.003","article-title":"Evidence for Selective Benefit of Sequential Treatment With Hypomethylating Agents in Patients With Myelodysplastic Syndrome","volume":"17","author":"Apuri","year":"2017","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.leukres.2015.02.004","article-title":"Outcome of Patients with High Risk Myelodysplastic Syndrome (MDS) and Advanced Chronic Myelomonocytic Leukemia (CMML) Treated with Decitabine after Azacitidine Failure","volume":"39","author":"Harel","year":"2015","journal-title":"Leuk. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1080\/10428190701882146","article-title":"Activity of Decitabine in Patients with Myelodysplastic Syndrome Previously Treated with Azacitidine","volume":"49","author":"Borthakur","year":"2008","journal-title":"Leuk. Lymphoma"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.3109\/10428194.2014.966708","article-title":"Lack of Objective Response of Myelodysplastic Syndromes and Acute Myeloid Leukemia to Decitabine after Failure of Azacitidine","volume":"56","author":"Duong","year":"2014","journal-title":"Leuk. Lymphoma"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Pandit, B., and Royzen, M. (2022). Recent Development of Prodrugs of Gemcitabine. Genes, 13.","DOI":"10.3390\/genes13030466"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Buocikova, V., Tyciakova, S., Pilalis, E., Mastrokalou, C., Urbanova, M., Matuskova, M., Demkova, L., Medova, V., Longhin, E.M., and Rund\u00e9n-Pran, E. (2022). Decitabine-Induced DNA Methylation-Mediated Transcriptomic Reprogramming in Human Breast Cancer Cell Lines; the Impact of DCK Overexpression. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.991751"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1007\/s40262-020-00934-7","article-title":"Intracellular Pharmacokinetics of Pyrimidine Analogues Used in Oncology and the Correlation with Drug Action","volume":"59","author":"Derissen","year":"2020","journal-title":"Clin. Pharmacokinet."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Vadeikien\u0117, R., Jak\u0161tys, B., Ugenskien\u0117, R., \u0160atkauskas, S., and Juozaityt\u0117, E. (2022). Systemic Optimization of Gene Electrotransfer Protocol Using Hard-to-Transfect UT-7 Cell Line as a Model. Biomedicines, 10.","DOI":"10.3390\/biomedicines10112687"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1038\/s44319-025-00385-w","article-title":"A CRISPR-Cas9 screen reveals genetic determinants of the cellular response to decitabine","volume":"26","author":"Zhang","year":"2025","journal-title":"Embo Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1158\/1535-7163.MCT-19-0745","article-title":"Decitabine Response in Breast Cancer Requires Efficient Drug Processing and Is Not Limited by Multidrug Resistance","volume":"19","author":"Dahn","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3388","DOI":"10.1038\/s41375-020-0973-z","article-title":"Distinct and overlapping mechanisms of resistance to azacytidine and guadecitabine in acute myeloid leukemia","volume":"34","author":"Gruber","year":"2020","journal-title":"Leukemia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1182\/blood.V85.5.1188.bloodjournal8551188","article-title":"Transfection of wild-type deoxycytidine kinase (dck) cDNA into an AraC- and DAC-resistant rat leukemic cell line of clonal origin fully restores drug sensitivity","volume":"85","author":"Stegmann","year":"1995","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.bbrc.2015.07.080","article-title":"Acquisition of chemoresistance to gemcitabine is induced by a loss-of-function missense mutation of DCK","volume":"464","author":"Nakano","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Qin, T., Castoro, R., El Ahdab, S., Jelinek, J., Wang, X., Si, J., Shu, J., He, R., Zhang, N., and Chung, W. (2011). Mechanisms of Resistance to Decitabine in the Myelodysplastic Syndrome. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023372"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.leukres.2014.08.016","article-title":"The HENT1 and DCK Genes Underlie the Decitabine Response in Patients with Myelodysplastic Syndrome","volume":"39","author":"Wu","year":"2015","journal-title":"Leuk. Res."},{"key":"ref_44","first-page":"1","article-title":"High Expression of the Human Equilibrative Nucleoside Transporter 1 Gene Predicts a Good Response to Decitabine in Patients with Myelodysplastic Syndrome","volume":"16","author":"Wu","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1021\/jm401853a","article-title":"Application of ProTide Technology to Gemcitabine: A Successful Approach to Overcome the Key Cancer Resistance Mechanisms Leads to a New Agent (NUC-1031) in Clinical Development","volume":"57","author":"Slusarczyk","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Daifuku, R., Koratich, M., and Stackhouse, M. (2018). Vitamin E Phosphate Nucleoside Prodrugs: A Platform for Intracellular Delivery of Monophosphorylated Nucleosides. Pharmaceuticals, 11.","DOI":"10.3390\/ph11010016"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/s41416-018-0244-1","article-title":"Anti-Tumour Activity of a First-in-Class Agent NUC-1031 in Patients with Advanced Cancer: Results of a Phase I Study","volume":"119","author":"Blagden","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/BF00694338","article-title":"Chemotherapy of L1210 and L1210\/ARA-C Leukemia with 5-Aza-2\u2032-Deoxycytidine and 3-Deazauridine","volume":"25","author":"Momparler","year":"1989","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1080\/15257770.2015.1124998","article-title":"Purification, Activity, and Expression Levels of Two Uridine-Cytidine Kinase Isoforms in Neuroblastoma Cell Lines","volume":"35","author":"Meinsma","year":"2016","journal-title":"Nucleosides Nucleotides Nucleic Acids"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5083\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:40:13Z","timestamp":1760031613000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,25]]},"references-count":49,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26115083"],"URL":"https:\/\/doi.org\/10.3390\/ijms26115083","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,25]]}}}