{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:03:15Z","timestamp":1789556595128,"version":"build-2803163510"},"reference-count":83,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The recognition of myelodysplastic syndrome\/acute myeloid leukemia (MDS\/AML) as a distinct overlap entity by the International Consensus Classification (ICC) has introduced new challenges in prognostication and therapeutic decision-making. Defined by 10\u201319% blasts in the absence of AML-defining genetic abnormalities, MDS\/AML occupies a biological continuum between myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) and is characterized by unique molecular features, patterns of clonal evolution, and clinical behavior that are not fully captured by prognostic systems originally developed for either disease. Consequently, the emergence of this entity has renewed interest in how existing classification and risk stratification frameworks should be applied to overlap disease. This review examines the biological basis of MDS\/AML and critically evaluates the strengths and limitations of the Molecular International Prognostic Scoring System (IPSS-M) and the European LeukemiaNet (ELN) classifications. Available evidence supports IPSS-M as the preferred framework for baseline disease-specific prognostic assessment, with preserved prognostic discrimination in this entity. In contrast, direct application of ELN 2022 results in substantial adverse-risk compression and limited prognostic discrimination. Emerging evidence suggests that disease-specific recalibration and treatment-contextual frameworks, including ELN 2022 modified and ELN 2024 Less-Intensive, may provide additional information, although validation specifically in MDS\/AML remains limited and largely retrospective. Collectively, current evidence supports a complementary rather than competitive approach. IPSS-M should provide the disease-specific prognostic foundation, whereas ELN-based assessment may add AML-oriented molecular and treatment-contextual information relevant to therapeutic planning. Neither framework should independently determine treatment intensity. Instead, optimal management should integrate disease-specific prognosis with patient fitness and transplant eligibility, molecular characteristics, treatment context, and dynamic response assessment. Emerging approaches incorporating clonal hierarchy, single-cell analysis, epigenomic and multi-omic profiling, measurable residual disease, and artificial intelligence (AI)- and machine learning (ML)-based predictive models may further refine prognostic assessment, improve prediction of treatment response, and facilitate increasingly individualized therapeutic strategies in MDS\/AML, although their clinical application remains investigational.<\/jats:p>","DOI":"10.3390\/cancers18182993","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:09:17Z","timestamp":1789553357000},"page":"2993","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ELN vs. IPSS-M in MDS\/AML: Which Prognostic System Should Guide Clinical Decision-Making?"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0911-6311","authenticated-orcid":false,"given":"Maria","family":"Liga","sequence":"first","affiliation":[{"name":"Hematology Division and Bone Marrow Transplantation Unit, Institute of Cell Therapy, University of Patras, 26504 Rio, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeliki N.","family":"Georgopoulou","sequence":"additional","affiliation":[{"name":"Hematology Division and Bone Marrow Transplantation Unit, Institute of Cell Therapy, University of Patras, 26504 Rio, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Tsokanas","sequence":"additional","affiliation":[{"name":"Hematology Division and Bone Marrow Transplantation Unit, Institute of Cell Therapy, University of Patras, 26504 Rio, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3097-2532","authenticated-orcid":false,"given":"Alexandros","family":"Spyridonidis","sequence":"additional","affiliation":[{"name":"Hematology Division and Bone Marrow Transplantation Unit, Institute of Cell Therapy, University of Patras, 26504 Rio, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassiliki T.","family":"Labropoulou","sequence":"additional","affiliation":[{"name":"Hematology Division, Department of Internal Medicine, University Hospital of Patras, University of Patras, 26504 Rio, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"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","first-page":"323","DOI":"10.1182\/blood.2021011304","article-title":"Distinguishing AML from MDS: A fixed blast percentage may no longer be optimal","volume":"139","author":"Estey","year":"2022","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/nrc.2016.112","article-title":"The genetics of myelodysplastic syndrome: From clonal haematopoiesis to secondary leukaemia","volume":"17","author":"Sperling","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1182\/blood-2018-10-844621","article-title":"Genetics of MDS","volume":"133","author":"Ogawa","year":"2019","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1182\/blood.2023023727","article-title":"Molecular taxonomy of myelodysplastic syndromes and its clinical implications","volume":"144","author":"Bernard","year":"2024","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/s41571-026-01141-2","article-title":"A 2026 update on myelodysplastic neoplasms: Current state, challenges and future directions","volume":"23","author":"Bewersdorf","year":"2026","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/MOH.0000000000000752","article-title":"Molecular landscape of myelodysplastic neoplasms in disease classification and prognostication","volume":"30","author":"Maggioni","year":"2023","journal-title":"Curr. Opin. Hematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"113905","DOI":"10.1016\/j.biopha.2022.113905","article-title":"Myelodysplastic neoplasms: An overview on diagnosis, risk-stratification, molecular pathogenesis, and treatment","volume":"156","author":"Marques","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1182\/blood.2022015850","article-title":"International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: Integrating morphologic, clinical, and genomic data","volume":"140","author":"Arber","year":"2022","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00428-022-03417-1","article-title":"The International Consensus Classification of myelodysplastic syndromes and related entities","volume":"482","author":"Hasserjian","year":"2023","journal-title":"Virchows Arch."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1038\/s41375-023-02004-w","article-title":"Risk assessment according to IPSS-M is superior to AML ELN risk classification in MDS\/AML overlap patients defined by ICC","volume":"37","author":"Huber","year":"2023","journal-title":"Leukemia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1182\/blood.2025030816","article-title":"Azacitidine to treat measurable residual disease in patients with MDS\/AML: Final long-term results of the RELAZA2 trial","volume":"147","author":"Platzbecker","year":"2026","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"106077","DOI":"10.1016\/j.humpath.2026.106077","article-title":"Navigating diagnostic shifts: A comparative review of the WHO 5th edition and ICC 2022 classifications of myeloid neoplasms","volume":"169","author":"Weinberg","year":"2026","journal-title":"Hum. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e70174","DOI":"10.1002\/hon.70174","article-title":"Comparative Analysis of ICC and WHO Classifications Reveals Molecular and Clinical Convergence Between AML-MR and MDS\/AML","volume":"44","author":"Wei","year":"2026","journal-title":"Hematol. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1002\/ajh.26799","article-title":"Clinico-genetic and prognostic analyses of 716 patients with primary myelodysplastic syndrome and myelodysplastic syndrome\/acute myeloid leukemia based on the 2022 International Consensus Classification","volume":"98","author":"Lee","year":"2023","journal-title":"Am. J. Hematol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41408-026-01456-4","article-title":"Prognostic implications of genetic and transcriptomic abnormalities in MDS according to IPSS-R, IPSS-M, and the International Consensus Classification","volume":"16","author":"Lee","year":"2026","journal-title":"Blood Cancer J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1182\/bloodadvances.2025018408","article-title":"MDS\/AML and AML with myelodysplasia-related gene mutations: Clinical and molecular similarities","volume":"10","author":"Boertjes","year":"2026","journal-title":"Blood Adv."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/ajh.70296","article-title":"Distinctive Molecular Risk Factors Between MDS and MDS\/AML Defined by ICC","volume":"101","author":"Zhang","year":"2026","journal-title":"Am. J. Hematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1056\/EVIDoa2200008","article-title":"Molecular International Prognostic Scoring System for Myelodysplastic Syndromes","volume":"1","author":"Bernard","year":"2022","journal-title":"NEJM Evid."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/j.1365-2141.1982.tb08475.x","article-title":"Proposals for the classification of the myelodysplastic syndromes","volume":"51","author":"Bennett","year":"1982","journal-title":"Br. J. Haematol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1056\/NEJMoa1106968","article-title":"Clonal Architecture of Secondary Acute Myeloid Leukemia","volume":"366","author":"Walter","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/ng.3742","article-title":"Dynamics of clonal evolution in myelodysplastic syndromes","volume":"49","author":"Makishima","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/s41586-018-0317-6","article-title":"Prediction of acute myeloid leukaemia risk in healthy individuals","volume":"559","author":"Abelson","year":"2018","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"312","DOI":"10.3324\/haematol.2023.284947","article-title":"Genome sequencing in the management of myelodysplastic syndromes and related disorders","volume":"110","author":"Cazzola","year":"2025","journal-title":"Haematologica"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5297","DOI":"10.1182\/bloodadvances.2024013685","article-title":"Beat-AML 2024 ELN-refined risk stratification for older adults with newly diagnosed AML given lower-intensity therapy","volume":"8","author":"Hoff","year":"2024","journal-title":"Blood Adv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1182\/blood.V89.6.2079","article-title":"International Scoring System for Evaluating Prognosis in Myelodysplastic Syndromes","volume":"89","author":"Greenberg","year":"1997","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1182\/blood-2012-03-420489","article-title":"Revised International Prognostic Scoring System for Myelodysplastic Syndromes","volume":"120","author":"Greenberg","year":"2012","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1182\/blood.2024025409","article-title":"Genetic risk classification for adults with AML receiving less-intensive therapies: The 2024 ELN recommendations","volume":"144","author":"DiNardo","year":"2024","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6239","DOI":"10.1182\/blood-2011-09-377275","article-title":"Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic\/myeloproliferative neoplasms","volume":"118","author":"Malcovati","year":"2011","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","article-title":"Genomic Classification and Prognosis in Acute Myeloid Leukemia","volume":"374","author":"Papaemmanuil","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1182\/blood.2021014472","article-title":"Molecular characterization of mutant TP53 acute myeloid leukemia and high-risk myelodysplastic syndrome","volume":"139","author":"Grob","year":"2022","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1038\/s41591-020-1008-z","article-title":"Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes","volume":"26","author":"Bernard","year":"2020","journal-title":"Nat. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e70164","DOI":"10.1002\/hem3.70164","article-title":"Long-term follow-up and combined Phase 2 results of eprenetapopt and azacitidine in patients with TP53 mutant MDS\/AML","volume":"9","author":"Sallman","year":"2025","journal-title":"HemaSphere"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s40364-024-00579-9","article-title":"p53 biology and reactivation for improved therapy in MDS and AML","volume":"12","author":"Zawacka","year":"2024","journal-title":"Biomark. Res."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Giuliani, A.L., Oliviero, F., Georgantzinos, E., and Karantanos, T. (2025). Molecular and Clinical Insights into TP53-Mutated MDS and AML. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262210818"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1182\/bloodadvances.2025016336","article-title":"Can we harmonize classification of TP53 mutant MDS\/AML?","volume":"9","author":"Sallman","year":"2025","journal-title":"Blood Adv."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1182\/bloodadvances.2024014499","article-title":"TP53-mutant variant allele frequency and cytogenetics determine prognostic groups in MDS\/AML for transplantation","volume":"9","author":"Lontos","year":"2025","journal-title":"Blood Adv."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3347","DOI":"10.1182\/bloodadvances.2025018188","article-title":"Validation of ICC hierarchical classification in secondary AML","volume":"10","author":"Attardi","year":"2026","journal-title":"Blood Adv."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/leu.2013.336","article-title":"Landscape of genetic lesions in 944 patients with myelodysplastic syndromes","volume":"28","author":"Haferlach","year":"2013","journal-title":"Leukemia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3616","DOI":"10.1182\/blood-2013-08-518886","article-title":"Clinical and biological implications of driver mutations in myelodysplastic syndromes","volume":"122","author":"Papaemmanuil","year":"2013","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2496","DOI":"10.1056\/NEJMoa1013343","article-title":"Clinical Effect of Point Mutations in Myelodysplastic Syndromes","volume":"364","author":"Bejar","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.1200\/JCO.22.01784","article-title":"Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes","volume":"41","author":"Sauta","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1182\/blood-2022-170878","article-title":"Validation of the Molecular International Prognostic Scoring System (IPSS-M) Risk Stratification Model for Myelodysplastic Syndromes","volume":"140","author":"Aguirre","year":"2022","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/s41375-023-01831-1","article-title":"Risk prediction in MDS: Independent validation of the IPSS-M\u2014Ready for routine?","volume":"37","author":"Baer","year":"2023","journal-title":"Leukemia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1182\/blood.2022018896","article-title":"Validation of the Molecular International Prognostic Scoring System in patients with myelodysplastic syndromes","volume":"141","author":"Kewan","year":"2023","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1182\/blood-2016-08-733196","article-title":"Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel","volume":"129","author":"Estey","year":"2017","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1182\/blood-2023-179822","article-title":"Modification of the ELN Classification 2022 Refines Risk Assessment in MDS\/AML Patients","volume":"142","author":"Huber","year":"2023","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2788","DOI":"10.1182\/blood.2024026925","article-title":"Refined ELN 2024 risk stratification improves survival prognostication following venetoclax-based therapy in AML","volume":"144","author":"Lachowiez","year":"2024","journal-title":"Blood"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Hu, J., Shuai, X., Guo, Y., Gong, Y., and Ma, H. (2026). Prognostic Validation of IPSS-M Versus ELN 2022\/2024 in MDS\/AML Patients: A Survival and Treatment Response Analysis. Eur. J. Haematol., 1\u20139.","DOI":"10.1111\/ejh.70273"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"100212","DOI":"10.1016\/j.bneo.2026.100212","article-title":"Treatment-specific prognostic performance of ELN 2022, ELN 2024, and Beat AML 2024: A real-world AML validation study","volume":"3","author":"Kewan","year":"2026","journal-title":"Blood Neoplasia"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1056\/NEJMoa2012971","article-title":"Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia","volume":"383","author":"DiNardo","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Stempel, J.M., Kewan, T., and Zeidan, A.M. (2025). Advances and Challenges in the Management of Myelodysplastic Syndromes. Cancers, 17.","DOI":"10.3390\/cancers17152469"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1002\/ajh.27246","article-title":"Long-term follow-up of VIALE-A: Venetoclax and azacitidine in chemotherapy-ineligible untreated acute myeloid leukemia","volume":"99","author":"Pratz","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1182\/blood-2013-03-492884","article-title":"Diagnosis and treatment of primary myelodysplastic syndromes in adults: Recommendations from the European LeukemiaNet","volume":"122","author":"Malcovati","year":"2013","journal-title":"Blood"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1182\/blood.2024025464","article-title":"Efficacy and safety of venetoclax plus azacitidine for patients with treatment-naive high-risk myelodysplastic syndromes","volume":"145","author":"Garcia","year":"2025","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"939.e1","DOI":"10.1016\/j.jtct.2026.04.002","article-title":"Multicenter Analysis of Transplant Outcomes for the Newly Defined MDS\/AML Entity in the 2022 ICC: Risk Stratification and Comparison with AML","volume":"32","author":"Ru","year":"2026","journal-title":"Transplant. Cell. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1200\/JCO.2013.52.3381","article-title":"Somatic mutations predict poor outcome in patients with myelodysplastic syndrome after hematopoietic stem-cell transplantation","volume":"32","author":"Bejar","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1182\/blood-2005-05-2004","article-title":"Hematopoietic cell transplantation (HCT)-specific comorbidity index: A new tool for risk assessment before allogeneic HCT","volume":"106","author":"Sorror","year":"2005","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1182\/blood.2025031480","article-title":"2025 update on MRD in acute myeloid leukemia: A consensus document from the ELN-DAVID MRD Working Party","volume":"147","author":"Cloos","year":"2026","journal-title":"Blood"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1002\/ajh.27259","article-title":"Relative Prognostic Value of Flow Cytometric Measurable Residual Disease before Allogeneic Hematopoietic Cell Transplantation for Adults with MDS\/AML or AML","volume":"99","author":"Orvain","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"106555","DOI":"10.1016\/j.leukres.2021.106555","article-title":"A systematic review of higher-risk myelodysplastic syndromes clinical trials to determine the benchmark of azacitidine and explore alternative endpoints for overall survival","volume":"104","author":"Garcia","year":"2021","journal-title":"Leuk. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"26","DOI":"10.21037\/atm-2026-1-0019","article-title":"Breaking through the azacitidine plateau?\u2014Venetoclax in high-risk myelodysplastic syndrome","volume":"14","author":"An","year":"2026","journal-title":"Ann. Transl. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41408-026-01543-6","article-title":"Outcomes of patients with higher-risk myelodysplastic syndromes\/neoplasms treated with hypomethylating agents + venetoclax\u2014An analysis from the International Consortium for MDS (icMDS) VALIDATE database","volume":"16","author":"Bewersdorf","year":"2026","journal-title":"Blood Cancer J."},{"key":"ref_66","unstructured":"(2026, August 23). CertainT-1: CER-1236 in Patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), and Myelofibrosis (MF) (NCT06834282). Available online: https:\/\/www.ancora.ai\/en\/details\/NCT06834282."},{"key":"ref_67","unstructured":"(2026, August 23). Regorafenib in Combination with Venetoclax and Azacitidine for the Treatment of Patients with Relapsed or Refractory Acute Myeloid Leukemia. Clinical Research Trial Listing. Available online: https:\/\/www.trialx.com\/clinical-trials\/listings\/307664\/regorafenib-in-combination-with\/."},{"key":"ref_68","unstructured":"(2026, August 23). Study Details|NCT06285890|Phase I Study of HC-7366 for Acute Myeloid Leukemia|ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06285890."},{"key":"ref_69","unstructured":"(2026, August 23). Testing the Anti-Cancer Drug, Cirtuvivint, and Its Combination with ASTX727 to Improve Outcomes in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes. Available online: https:\/\/clin.larvol.com\/trial-detail\/NCT06484062."},{"key":"ref_70","unstructured":"(2026, August 23). Phase I Study of Q702 with Azacitidine and Venetoclax for Relapsed or Refractory Acute Myeloid Leukemia. Available online: https:\/\/www.mdanderson.org\/patients-family\/diagnosis-treatment\/clinical-trials\/clinical-trials-index\/clinical-trials-detail.ID2024-0178.html."},{"key":"ref_71","unstructured":"(2026, August 23). Study Details|NCT05358808|ACHIEVE\u2014Efficacy and Effectiveness of Adoptive Cellular tHerapy wIth Ex-Vivo Expanded Allogeneic \u03b3\u03b4 T-lymphocytes (TCB008) for Patients with Refractory or Relapsed Acute Myeloid Leukaemia (AML)|ClinicalTrials.gov, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05358808."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5386","DOI":"10.1038\/s41467-019-13001-y","article-title":"Invariant patterns of clonal succession determine specific clinical features of myelodysplastic syndromes","volume":"10","author":"Nagata","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/s41591-018-0267-4","article-title":"Myelodysplastic syndrome progression to acute myeloid leukemia at the stem cell level","volume":"25","author":"Chen","year":"2019","journal-title":"Nat. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1158\/2643-3230.BCD-21-0128","article-title":"Distinct Patterns of Clonal Evolution Drive Myelodysplastic Syndrome Progression to Secondary Acute Myeloid Leukemia","volume":"3","author":"Guess","year":"2022","journal-title":"Blood Cancer Discov."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41586-020-2864-x","article-title":"Single-cell mutation analysis of clonal evolution in myeloid malignancies","volume":"587","author":"Miles","year":"2020","journal-title":"Nature"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"S\u00f8rensen, E.F., Arv\u00e9, C., Gronlund, J.K., Melsvik, D., Pold, J.A., Knudsen, M., Thorsen, K., Aggerholm, A., and Ommen, H.B. (2026). Single-Cell Multi-Omics Identifies Measurable Residual Disease Targets Among Myelodysplasia- and Clonal Hematopoiesis-Related Genes in Acute Myeloid Leukemia. Cancers, 18.","DOI":"10.3390\/cancers18050787"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5901","DOI":"10.1038\/ncomms6901","article-title":"Combining gene mutation with gene expression data improves outcome prediction in myelodysplastic syndromes","volume":"6","author":"Gerstung","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1038\/s41375-026-03015-z","article-title":"Single-cell DNA methylation analysis uncovers epigenetic pathways in the transformation of MDS to AML","volume":"40","author":"Yassine","year":"2026","journal-title":"Leukemia"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1038\/s41588-025-02321-z","article-title":"Rapid epigenomic classification of acute leukemia","volume":"57","author":"Steinicke","year":"2025","journal-title":"Nat. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"101340","DOI":"10.1016\/j.blre.2025.101340","article-title":"Artificial intelligence in myeloid malignancies: Clinical applications of machine learning in myelodysplastic syndromes and acute myeloid Leukemia","volume":"74","author":"Lanino","year":"2025","journal-title":"Blood Rev."},{"key":"ref_81","first-page":"2047","article-title":"Consensus proposal for revised International Working Group 2023 response criteria for higher-risk myelodysplastic syndromes","volume":"141","author":"Zeidan","year":"2023","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1182\/blood.2020010603","article-title":"Machine learning integrates genomic signatures for subclassification beyond primary and secondary acute myeloid leukemia","volume":"138","author":"Awada","year":"2021","journal-title":"Blood"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"536","DOI":"10.3324\/haematol.2024.286340","article-title":"Artificial intelligence-based Myelodysplastic Syndromes Score, 2022 classifications, and the Molecular International Prognostic Scoring System: A perfect match","volume":"110","author":"Clichet","year":"2025","journal-title":"Haematologica"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/18\/2993\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:16:09Z","timestamp":1789553769000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/18\/2993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":83,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cancers18182993"],"URL":"https:\/\/doi.org\/10.3390\/cancers18182993","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}