{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T16:34:12Z","timestamp":1786725252599,"version":"build-2736575974"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Fluorescence in situ hybridization (FISH) is an established component of the diagnostic and prognostic workup of hematologic malignancies. However, most evidence supporting FISH interpretation originates from treatment-na\u00efve diagnostic cohorts, providing limited insight into how cytogenetic findings evolve during longitudinal disease monitoring and therapeutic exposure. We retrospectively analyzed 1357 consecutive FISH assays performed in 1092 patients with hematologic malignancies between 2019 and 2023. Methods: Multivariable logistic regression identified predictors of aberration detection, while longitudinal analyses explored temporal changes in cytogenetic profiles among serially monitored patients. Observed abnormality rates were compared with published diagnostic benchmarks. Results: The cohort had a median age of 68 years and was predominantly composed of patients with myelodysplastic\/myeloproliferative neoplasms (27.2%), multiple myeloma (26.9%), and chronic lymphocytic leukemia (21.6%). Overall, 29.2% of informative assays revealed cytogenetic abnormalities. Clinical indication was the strongest predictor of aberration detection. Compared with diagnostic samples, follow-up specimens showed significantly lower odds of abnormal findings (adjusted OR 0.48, 95% CI 0.36\u20130.64; p &lt; 0.001), whereas relapse samples demonstrated higher odds (adjusted OR 1.82, 95% CI 1.28\u20132.59; p = 0.001). Increasing age was independently associated with abnormal FISH results (adjusted OR per decade 1.24, 95% CI 1.12\u20131.38; p &lt; 0.001). Several canonical abnormalities occurred less frequently than expected from historical diagnostic series, including BCR::ABL1 within the chronic myeloid leukemia testing pathway and del(13q14) in both chronic lymphocytic leukemia and multiple myeloma. In contrast, del(17p), involving the TP53 locus, remained consistently represented across disease categories and was enriched in chronic lymphocytic leukemia relative to published diagnostic cohorts. Conclusions: Longitudinal assessment revealed increasing cytogenetic heterogeneity over time, with common lesions progressively declining and rare or complex abnormalities expanding from 16.3% to 36.7% of the observed cytogenetic landscape. The cytogenetic patterns detected by FISH in contemporary hematology practice are strongly associated with clinical context, disease stage, and treatment history; however, the cross-sectional and retrospective design precludes inference of causal influence. The divergence between real-world positivity rates and historical diagnostic benchmarks highlights the need for context-specific interpretation of cytogenetic findings. The persistence of TP53 loss across disease boundaries and the progressive diversification of aberrations over time underscore the dynamic nature of clonal evolution in hematologic malignancies.<\/jats:p>","DOI":"10.3390\/genes17080955","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T15:48:36Z","timestamp":1786722516000},"page":"955","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real-World Diagnostic Yield and Longitudinal Dynamics of Fluorescence In Situ Hybridization in Hematologic Malignancies: A Five-Year Retrospective Analysis of 1357 Patient Samples"],"prefix":"10.3390","volume":"17","author":[{"given":"Rosalba","family":"Fumo","sequence":"first","affiliation":[{"name":"Complex Operative Unit of Pathological Anatomy and Molecular Diagnostics, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, University of Salerno, Largo Citt\u00e0 di Ippocrate, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Scala","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Pathological Anatomy and Molecular Diagnostics, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, University of Salerno, Largo Citt\u00e0 di Ippocrate, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2455-5242","authenticated-orcid":false,"given":"Sara","family":"Gaeta","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Pathological Anatomy and Molecular Diagnostics, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, University of Salerno, Largo Citt\u00e0 di Ippocrate, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"D\u2019Ardia","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Pathological Anatomy and Molecular Diagnostics, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, University of Salerno, Largo Citt\u00e0 di Ippocrate, 84131 Salerno, Italy"},{"name":"Specialization School in Clinical Pathology and Clinical Biochemistry, Department of Medicine, Surgery, and Dentistry \u201cSchola Medica Salernitana\u201d, University of Salerno, Via Salvador Allende, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Infante","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Pathological Anatomy and Molecular Diagnostics, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, University of Salerno, Largo Citt\u00e0 di Ippocrate, 84131 Salerno, Italy"},{"name":"Specialization School in Clinical Pathology and Clinical Biochemistry, Department of Medicine, Surgery, and Dentistry \u201cSchola Medica Salernitana\u201d, University of Salerno, Via Salvador Allende, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Ciancia","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Pathological Anatomy and Molecular Diagnostics, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, University of Salerno, Largo Citt\u00e0 di Ippocrate, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Caputo","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Pathological Anatomy and Molecular Diagnostics, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, University of Salerno, Largo Citt\u00e0 di Ippocrate, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6675-0857","authenticated-orcid":false,"given":"Alessandra","family":"Rosati","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery, and Dentistry \u201cSchola Medica Salernitana\u201d, University of Salerno, Via Salvador Allende, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Serio","sequence":"additional","affiliation":[{"name":"Hematology and Transplant Center, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, University of Salerno, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5425-6878","authenticated-orcid":false,"given":"Antonio","family":"D\u2019Antonio","sequence":"additional","affiliation":[{"name":"Department of Pathology, PO del Mare, Via Enrico Russo, 80147 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7358-5925","authenticated-orcid":false,"given":"Pio","family":"Zeppa","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Pathological Anatomy and Molecular Diagnostics, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, University of Salerno, Largo Citt\u00e0 di Ippocrate, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6300-0604","authenticated-orcid":false,"given":"Massimiliano","family":"Chetta","sequence":"additional","affiliation":[{"name":"Complex Operative Unit of Pathological Anatomy and Molecular Diagnostics, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, University of Salerno, Largo Citt\u00e0 di Ippocrate, 84131 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","first-page":"13","article-title":"Appraisal of current technologies for the study of genetic alterations in hematologic malignancies with a focus on chromosome analysis and structural variants","volume":"36","author":"Salaverria","year":"2024","journal-title":"Med. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1002\/ajh.27443","article-title":"Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring","volume":"99","author":"Jabbour","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1002\/ajh.27359","article-title":"BCR::ABL1 digital PCR for treatment-free remission prediction in chronic myeloid leukemia patients: An individual participant data meta-analysis","volume":"99","author":"Kockerols","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/ajh.27546","article-title":"Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy","volume":"100","author":"Hallek","year":"2025","journal-title":"Am. J. Hematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1002\/ajh.27422","article-title":"Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management","volume":"99","author":"Rajkumar","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/j.1600-0609.2012.01790.x","article-title":"High-risk clonal evolution in chronic B-lymphocytic leukemia: Single-center interphase fluorescence in situ hybridization study and review of the literature","volume":"89","author":"Janssens","year":"2012","journal-title":"Eur. J. Haematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"591","DOI":"10.3324\/haematol.2023.283533","article-title":"Minor clone of del(17p) provides a reservoir for relapse in multiple myeloma","volume":"109","author":"Cui","year":"2024","journal-title":"Haematologica"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e685","DOI":"10.1016\/j.clml.2022.03.005","article-title":"Presentation and Impact of Double and Triple hit Cytogenetics in Patients with Multiple Myeloma in the Real World","volume":"22","author":"Singh","year":"2022","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"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":"86","DOI":"10.1038\/s41408-025-01286-w","article-title":"Guidelines for the testing and reporting of cytogenetic results for risk stratification of multiple myeloma: A report of the Cancer Genomics Consortium Plasma Cell Neoplasm Working Group","volume":"15","author":"Lu","year":"2025","journal-title":"Blood Cancer J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"703","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_12","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms","volume":"36","author":"Alaggio","year":"2022","journal-title":"Leukemia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/cyt.12132","article-title":"Fine needle aspiration cytology of lymphoproliferative lesions of the oral cavity","volume":"25","author":"Cozzolino","year":"2014","journal-title":"Cytopathology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1002\/cncy.21203","article-title":"Immunoglobulin heavy-chain fluorescence in situ hybridization-chromogenic in situ hybridization DNA probe split signal in the clonality assessment of lymphoproliferative processes on cytological samples","volume":"120","author":"Zeppa","year":"2012","journal-title":"Cancer Cytopathol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Xia, C., Liu, G., Liu, J., Ronaghy, A., Tadros, S., Wang, W., Fang, H., Zhang, S., Khoury, J.D., and Tang, Z. (2025). The Heterogeneity of 13q Deletions in Chronic Lymphocytic Leukemia: Diagnostic Challenges and Clinical Implications. Genes, 16.","DOI":"10.3390\/genes16030252"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1038\/s41375-025-02664-w","article-title":"2025 European LeukemiaNet recommendations for the management of chronic myeloid leukemia","volume":"39","author":"Apperley","year":"2025","journal-title":"Leukemia"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"(2024). ISCN 2024\u2014An International System for Human Cytogenomic Nomenclature (2024). Cytogenet. Genome. Res., 164, 1\u2013224.","DOI":"10.1159\/000538512"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Harrell, F.E. (2015). Regression Modeling Strategies: With Applications to Linear Models, Logistic and Ordinal Regression, and Survival Analysis, Springer. [2nd ed.].","DOI":"10.1007\/978-3-319-19425-7"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s10238-025-01707-x","article-title":"Development and validation of a nomogram risk prediction model for PICC-related thrombosis in children with hematological malignancies","volume":"25","author":"Fu","year":"2025","journal-title":"Clin. Exp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"107453","DOI":"10.1016\/j.cct.2024.107453","article-title":"An evaluation of confidence intervals for a cumulative proportion to enable decisions at interim reviews of single-arm trials","volume":"138","author":"Weir","year":"2024","journal-title":"Contemp. Clin. Trials."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"102513","DOI":"10.1016\/j.canep.2023.102513","article-title":"Lymphoid blood cancers, incidence and survival 2005\u20132023: A report from the UK\u2019s Haematological Malignancy Research Network","volume":"88","author":"Lamb","year":"2024","journal-title":"Cancer Epidemiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"104560","DOI":"10.1016\/j.critrevonc.2024.104560","article-title":"A systematic literature review on clonal evolution events preceding relapse in multiple myeloma","volume":"205","author":"Jakobsen","year":"2025","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_23","first-page":"3133","article-title":"Optical genome mapping reveals complex cytogenetic abnormalities in multiple myeloma","volume":"110","author":"Palacios","year":"2025","journal-title":"Haematologica"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12.e1","DOI":"10.1016\/j.jtct.2024.10.011","article-title":"Real-World Outcomes of Upfront Autologous Hematopoietic Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma with Deletion 17p","volume":"31","author":"Marcoux","year":"2025","journal-title":"Transplant. Cell Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/s41418-024-01391-6","article-title":"TP53: The unluckiest of genes?","volume":"32","author":"Joerger","year":"2025","journal-title":"Cell Death Differ."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"475","DOI":"10.4103\/ijmr.IJMR_2257_18","article-title":"Role of cytogenetic abnormalities detected by fluorescence in situ hybridization as a prognostic marker: Pathogenesis & clinical course in patients with B-chronic lymphocytic leukaemia","volume":"153","author":"Shetty","year":"2021","journal-title":"Indian J. Med. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.1038\/s41375-025-02756-7","article-title":"Clonal evolution and apoptosis resistance in myelodysplastic neoplasms and acute myeloid leukemia under treatment: Insights from integrative longitudinal profiling","volume":"39","author":"Mazzeo","year":"2025","journal-title":"Leukemia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1007\/s12185-025-04046-5","article-title":"Sequential occurrence of BCR::ABL1-negative MPN and CML and vice versa: Results from a real world cohort","volume":"122","author":"Schweneker","year":"2025","journal-title":"Int. J. Hematol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41408-018-0061-z","article-title":"Detailed analysis of clonal evolution and cytogenetic evolution patterns in patients with myelodysplastic syndromes (MDS) and related myeloid disorders","volume":"8","author":"Schanz","year":"2018","journal-title":"Blood Cancer J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6778","DOI":"10.1158\/1078-0432.CCR-11-0785","article-title":"The prognostic significance of various 13q14 deletions in chronic lymphocytic leukemia","volume":"17","author":"Ouillette","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/s41408-022-00724-3","article-title":"Myelodysplastic syndromes with del(5q): A real-life study of determinants of long-term outcomes and response to lenalidomide","volume":"12","author":"Gurnari","year":"2022","journal-title":"Blood Cancer J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1182\/bloodadvances.2023010435","article-title":"Monosomy 7\/del(7q) cause sensitivity to inhibitors of nicotinamide phosphoribosyltransferase in acute myeloid leukemia","volume":"8","author":"Eldfors","year":"2024","journal-title":"Blood Adv."},{"key":"ref_33","first-page":"e125157","article-title":"Therapeutic discovery for marrow failure with MDS predisposition using pluripotent stem cells","volume":"5","author":"Alexe","year":"2019","journal-title":"JCI Insight"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/ajh.27655","article-title":"TP53 -Mutated Myeloid Neoplasms: 2024 Update on Diagnosis, Risk-Stratification, and Management","volume":"100","author":"Shah","year":"2025","journal-title":"Am. J. Hematol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3779","DOI":"10.1007\/s00277-025-06452-5","article-title":"IGH\/IGK gene rearrangement in the diagnosis of B-cell non-Hodgkin lymphoma: Experience from three centers","volume":"104","author":"Yang","year":"2025","journal-title":"Ann. Hematol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101176","DOI":"10.1016\/j.tranon.2021.101176","article-title":"Low prevalence and independent prognostic role of del(11q) in Chinese patients with chronic lymphocytic leukemia","volume":"14","author":"Zou","year":"2021","journal-title":"Transl. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wang, X., An, W., Liu, C., Zhang, B., Chen, Y., Wan, Y., Li, X., Liu, L., Liu, F., and Zhang, L. (2025). Early BCR::ABL1 Reduction as a Predictor of Deep Molecular Response in Pediatric Chronic-Phase Chronic Myeloid Leukemia. Cancers, 17.","DOI":"10.3390\/cancers17243994"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104669","DOI":"10.1016\/j.exphem.2024.104669","article-title":"Inducible pluripotent stem cell models to study bone marrow failure and MDS predisposition syndromes","volume":"143","author":"Sahoo","year":"2025","journal-title":"Exp. Hematol."},{"key":"ref_39","first-page":"2893","article-title":"The initial molecular response predicts the deep molecular response but not treatment-free remission maintenance in a real-world chronic myeloid leukemia cohort","volume":"109","author":"Saugues","year":"2024","journal-title":"Haematologica"},{"key":"ref_40","first-page":"59","article-title":"Mantle cell lymphoma: From pathogenesis to treatment for 2024 and beyond","volume":"67","year":"2025","journal-title":"Panminerva Med."},{"key":"ref_41","first-page":"1304","article-title":"Clinical interrogation of TP53 aberrations and its impact on survival in patients with myeloid neoplasms","volume":"110","author":"Senapati","year":"2025","journal-title":"Haematologica"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s10020-025-01392-2","article-title":"Multi-hit TP53 confers the poorest survival in multiple myeloma in the era of novel therapies","volume":"32","author":"Nesnadna","year":"2025","journal-title":"Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/s41388-025-03300-8","article-title":"Deletion of 17p in cancers: Guilt by (p53) association","volume":"44","author":"Clark","year":"2025","journal-title":"Oncogene"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/8\/955\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T15:55:13Z","timestamp":1786722913000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/8\/955"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":43,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["genes17080955"],"URL":"https:\/\/doi.org\/10.3390\/genes17080955","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}