{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T20:24:10Z","timestamp":1773174250422,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Relapsed acute myeloid leukemia (AML) is often characterized by clonal evolution and acquired genomic abnormalities, which can inform prognosis and direct therapeutic decisions. The emergence of high-risk chromosomal rearrangements during relapse is of particular significance, yet the impact of rare and complex events remains poorly understood. This report details a case of relapsed AML that demonstrated rare MYC and MECOM rearrangements and additional features that were not observed at initial diagnosis, emphasizing the clinical relevance of serial cytogenetic assessments. Case Description: A 70-year-old man was initially diagnosed with AML, exhibiting monocytic differentiation, an 11q23 deletion involving KMT2A loss, and a U2AF1 mutation. After achieving remission with azacitidine and venetoclax, the patient relapsed within ten months, necessitating reevaluation and modification of therapy. Repeat cytogenetic analysis at relapse revealed a distinct t(3;8)(q26.2;q24.3) exhibiting MYC and MECOM rearrangements, features that were absent at initial diagnosis. Conclusions: This case underscores the importance of serial cytogenetic and molecular profiling in relapsed AML. The emergence of new abnormalities upon relapse suggested underlying genomic instability and clonal evolution. MYC rearrangements are notably rare in AML, especially with concurrent MECOM rearrangements, highlighting a unique feature of this case. The identification of novel abnormalities at relapse may carry prognostic and therapeutic significance and may be used to refine risk stratification. Thus, ongoing cytogenetic monitoring is essential to adapt management approaches in evolving disease contexts.<\/jats:p>","DOI":"10.3390\/diagnostics15182410","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T13:04:44Z","timestamp":1758546284000},"page":"2410","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Relapsed AML Case Featuring MYC and MECOM Rearrangements"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8634-2893","authenticated-orcid":false,"given":"Kevin A.","family":"Murgas","sequence":"first","affiliation":[{"name":"Medical Scientist Training Program, Stony Brook University Renaissance School of Medicine, Stony Brook, NY 11794, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0102-383X","authenticated-orcid":false,"suffix":"III","given":"Pons","family":"Materum","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stony Brook University Hospital, Stony Brook, NY 11794, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luke Z.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Stony Brook University Hospital, Stony Brook, NY 11794, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Rocha","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stony Brook University Hospital, Stony Brook, NY 11794, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Schuster","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Stony Brook University Hospital, Stony Brook, NY 11794, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tahmeena","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stony Brook University Hospital, Stony Brook, NY 11794, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5339-5347","authenticated-orcid":false,"given":"Carlos A.","family":"Tirado","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stony Brook University Hospital, Stony Brook, NY 11794, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1007\/s11864-022-01021-8","article-title":"Pathogenic Mechanisms in Acute Myeloid Leukemia","volume":"23","author":"Chakraborty","year":"2022","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_2","first-page":"1345","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 J. Am. Soc. Hematol."},{"key":"ref_3","unstructured":"Ozkan, E., and Lacerda, M.P. (2020). Genetics, Cytogenetic Testing and Conventional Karyotype, StatPearls Publishing."},{"key":"ref_4","unstructured":"National Comprehensive Cancer Network (NCCN) (2025). Clinical Practice Guidelines in Oncology (NCCN Guidelines\u00ae): Acute Myeloid Leukemia, NCCN. Available online: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/aml.pdf."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1002\/gcc.22806","article-title":"Clonal Evolution of Acute Myeloid Leukemia from Diagnosis to Relapse","volume":"58","author":"Vosberg","year":"2019","journal-title":"Genes. Chromosomes Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1038\/s41375-021-01153-0","article-title":"Genomic and Evolutionary Portraits of Disease Relapse in Acute Myeloid Leukemia","volume":"35","author":"Rapaport","year":"2021","journal-title":"Leukemia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/s12935-024-03368-4","article-title":"Comprehensive Insights into AML Relapse: Genetic Mutations, Clonal Evolution, and Clinical Outcomes","volume":"24","author":"Kim","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_8","first-page":"92","article-title":"A t (3; 8)(Q26. 2; Q24) Involving the EVI1 (MECOM) Gene","volume":"44","author":"Liu","year":"2018","journal-title":"J. Assoc. Genet. Technol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.jmoldx.2018.10.005","article-title":"T(3;8)(Q26.2;Q24) Often Leads to MECOM\/MYC Rearrangement and Is Commonly Associated with Therapy-Related Myeloid Neoplasms and\/or Disease Progression","volume":"21","author":"Tang","year":"2019","journal-title":"J. Mol. Diagn."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"106387","DOI":"10.1016\/j.leukres.2020.106387","article-title":"MECOM Rearrangement Involving the MYC Locus: Two Additional Patients with the Rare Translocation, t(3;8)(Q26.2;Q24), and Molecular Review","volume":"95","author":"Smith","year":"2020","journal-title":"Leuk. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1182\/blood-2024-208948","article-title":"Optical Genome Mapping As Standard-of-Care in Acute Leukemia: Diagnostic and Clinical Impacts 10 Months Post-Implementation","volume":"144","author":"McGinnis","year":"2024","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5927","DOI":"10.1182\/blood-2023-185524","article-title":"Cladribine and Low-Dose Cytarabine-Based Salvage Therapy for Relapsed\/Refractory AML in a Predominantly Venetoclax-Exposed Cohort","volume":"142","author":"Cheung","year":"2023","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.clml.2017.06.002","article-title":"FLAG-Ida Regimen as Bridge Therapy to Allotransplantation in Refractory\/Relapsed Acute Myeloid Leukemia Patients","volume":"17","author":"Delia","year":"2017","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/s41408-021-00557-6","article-title":"Predictors of Outcomes in Adults with Acute Myeloid Leukemia and KMT2A Rearrangements","volume":"11","author":"Issa","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_15","first-page":"1833","article-title":"KMT2A-Rearranged Leukemia: The Shapeshifter","volume":"140","author":"Iacobucci","year":"2022","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_16","first-page":"5077","article-title":"MYC Rearrangements in Myeloid Neoplasms","volume":"130","author":"Boddu","year":"2017","journal-title":"Blood"},{"key":"ref_17","first-page":"202","article-title":"C-MYC Amplification in AML","volume":"47","author":"Tang","year":"2021","journal-title":"J. Assoc. Genet. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Call, S.G., Duren, R.P., Panigrahi, A.K., Nguyen, L., Freire, P.R., Grimm, S.L., Coarfa, C., and Conneely, O.M. (2020). Targeting Oncogenic Super Enhancers in MYC-Dependent AML Using a Small Molecule Activator of NR4A Nuclear Receptors. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-59469-3"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.cell.2018.03.068","article-title":"Promoter of LncRNA Gene PVT1 Is a Tumor-Suppressor DNA Boundary Element","volume":"173","author":"Cho","year":"2018","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"145497","DOI":"10.1016\/j.gene.2021.145497","article-title":"PVT1: A Long Non-Coding RNA Recurrently Involved in Neoplasia-Associated Fusion Transcripts","volume":"779","author":"Tolomeo","year":"2021","journal-title":"Gene"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3890","DOI":"10.1200\/JCO.2010.29.2771","article-title":"Clinical, Molecular, and Prognostic Significance of WHO Type Inv(3)(Q21q26.2)\/t(3;3)(Q21;Q26.2) and Various Other 3q Abnormalities in Acute Myeloid Leukemia","volume":"28","author":"Lugthart","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_22","first-page":"224","article-title":"Atypical 3q26\/MECOM Rearrangements Genocopy Inv(3)\/t(3;3) in Acute Myeloid Leukemia","volume":"136","author":"Ottema","year":"2020","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cancergencyto.2007.05.007","article-title":"Aberrant EVI1 Expression in Acute Myeloid Leukemias Associated with the t(3;8)(Q26;Q24)","volume":"177","author":"Lennon","year":"2007","journal-title":"Cancer Genet. Cytogenet."},{"key":"ref_24","unstructured":"(2025, May 12). Pei Lin T(3;8)(Q26;Q24) PVT1\/MECOM. Available online: http:\/\/atlasgeneticsoncology.org\/haematological\/1463\/t(3;8)(q26;q24)-pvt1-mecom."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1159\/000529844","article-title":"Description of an Institutional Cohort of Myeloid Neoplasms Carrying ETV6-Locus Deletions or ETV6 Rearrangements","volume":"146","author":"Papadopoulou","year":"2023","journal-title":"Acta Haematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1172\/JCI91363","article-title":"The U2AF1 S34F Mutation Induces Lineage-Specific Splicing Alterations in Myelodysplastic Syndromes","volume":"127","author":"Yip","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/s41408-023-00922-7","article-title":"U2AF1 Pathogenic Variants in Myeloid Neoplasms and Precursor States: Distribution of Co-Mutations and Prognostic Heterogeneity","volume":"13","author":"Badar","year":"2023","journal-title":"Blood Cancer J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1038\/modpathol.2017.19","article-title":"3q26. 2\/EVI1 Rearrangement Is Associated with Poor Prognosis in Classical Philadelphia Chromosome-Negative Myeloproliferative Neoplasms","volume":"30","author":"Hu","year":"2017","journal-title":"Mod. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cancergen.2019.03.002","article-title":"Deciphering the Complexities of MECOM Rearrangement-Driven Chromosomal Aberrations","volume":"233","author":"Tang","year":"2019","journal-title":"Cancer Genet."},{"key":"ref_30","first-page":"109","article-title":"MECOM: A Very Interesting Gene Involved Also in Lymphoid Malignancies","volume":"45","author":"Liu","year":"2019","journal-title":"J. Assoc. Genet. Technol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1080\/10428194.2018.1464158","article-title":"MYC Protein Expression Is an Important Prognostic Factor in Acute Myeloid Leukemia","volume":"60","author":"Ohanian","year":"2019","journal-title":"Leuk Lymphoma"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0165-4608(87)90251-2","article-title":"A Case of Myelodysplastic Syndrome with High Platelet Counts and at (3; 8)(Q26; Q24)","volume":"27","author":"Mertens","year":"1987","journal-title":"Cancer Genet. Cytogenet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/gcc.22341","article-title":"Complex Chromosomal Rearrangements Leading to MECOM Overexpression Are Recurrent in Myeloid Malignancies with Various 3q Abnormalities","volume":"55","author":"Baldazzi","year":"2016","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3343\/alm.2024.0477","article-title":"Abnormalities in Chromosomes 5 and 7 in Myelodysplastic Syndrome and Acute Myeloid Leukemia","volume":"45","author":"Kendrick","year":"2025","journal-title":"Ann. Lab. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1182\/bloodadvances.2022007583","article-title":"Optical Genome Mapping in Acute Myeloid Leukemia: A Multicenter Evaluation","volume":"7","author":"Levy","year":"2023","journal-title":"Blood Adv."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1002\/ajh.27175","article-title":"A Framework for the Clinical Implementation of Optical Genome Mapping in Hematologic Malignancies","volume":"99","author":"Levy","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3556","DOI":"10.1182\/bloodadvances.2024015734","article-title":"Prognostic Significance of Monocytic-like Phenotype in Patients with AML Treated with Venetoclax and Azacytidine","volume":"9","author":"Zhao","year":"2025","journal-title":"Blood Adv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1182\/blood.2024024944","article-title":"Genetic Risk Stratification and Outcomes among Treatment-Naive Patients with AML Treated with Venetoclax and Azacitidine","volume":"144","author":"Pratz","year":"2024","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1200\/JCO.24.00826","article-title":"Menin Inhibition with Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101)","volume":"43","author":"Issa","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1182\/bloodadvances.2024014279","article-title":"Long-Term Real-World Evidence of CPX-351 of High-Risk Patients with AML Identified High Rate of Negative MRD and Prolonged OS","volume":"9","author":"Cluzeau","year":"2025","journal-title":"Blood Adv."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Leisch, M., Jansko, B., Zaborsky, N., Greil, R., and Pleyer, L. (2019). Next Generation Sequencing in AML\u2014on the Way to Becoming a New Standard for Treatment Initiation and\/or Modulation?. Cancers, 11.","DOI":"10.3390\/cancers11020252"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/18\/2410\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:47:06Z","timestamp":1760035626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/18\/2410"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,22]]},"references-count":41,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["diagnostics15182410"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15182410","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,22]]}}}