{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T18:54:41Z","timestamp":1772304881728,"version":"3.50.1"},"reference-count":25,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:00:00Z","timestamp":1714176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Carlos III Health Institute of the Ministry of Science","award":["PI19\/00792"],"award-info":[{"award-number":["PI19\/00792"]}]},{"name":"Carlos III Health Institute of the Ministry of Science","award":["PI22\/00603"],"award-info":[{"award-number":["PI22\/00603"]}]},{"name":"Carlos III Health Institute of the Ministry of Science","award":["AC20\/00066"],"award-info":[{"award-number":["AC20\/00066"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Cytogenetic studies are essential in the diagnosis and follow up of patients with bone marrow failure syndromes (BMFSs), but obtaining good quality results is often challenging due to hypocellularity. Optical Genome Mapping (OGM), a novel technology capable of detecting most types chromosomal structural variants (SVs) at high resolution, is being increasingly used in many settings, including hematologic malignancies. Herein, we compared conventional cytogenetic techniques to OGM in 20 patients with diverse BMFSs. Twenty metaphases for the karyotype were only obtained in three subjects (15%), and no SVs were found in any of the samples. One patient with culture failure showed a gain in chromosome 1q by fluorescence in situ hybridization, which was confirmed by OGM. In contrast, OGM provided good quality results in all subjects, and SVs were detected in 14 of them (70%), mostly corresponding to cryptic submicroscopic alterations not observed by standard techniques. Therefore, OGM emerges as a powerful tool that provides complete and evaluable results in hypocellular BMFSs, reducing multiple tests into a single assay and overcoming some of the main limitations of conventional techniques. Furthermore, in addition to confirming the abnormalities detected by conventional techniques, OGM found new alterations beyond their detection limits.<\/jats:p>","DOI":"10.3390\/genes15050559","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T10:33:31Z","timestamp":1714559611000},"page":"559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Optical Genome Mapping as a New Tool to Overcome Conventional Cytogenetics Limitations in Patients with Bone Marrow Failure"],"prefix":"10.3390","volume":"15","author":[{"given":"June","family":"Iriondo","sequence":"first","affiliation":[{"name":"Hematology and Hemotherapy Unit, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"},{"name":"Biomedical Research Foundation, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Laboratory and Clinical Analysis Department, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4115-9598","authenticated-orcid":false,"given":"Josune","family":"Zubicaray","sequence":"additional","affiliation":[{"name":"Hematology and Hemotherapy Unit, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"},{"name":"Biomedical Research Foundation, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1566-8145","authenticated-orcid":false,"given":"Jorge","family":"Garcia-Martinez","sequence":"additional","affiliation":[{"name":"Pediatric Onco-Hematology Department, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"},{"name":"Health Research Institute at Hospital de La Princesa (IIS-Princesa), 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorea","family":"Abad","sequence":"additional","affiliation":[{"name":"Laboratory and Clinical Analysis Department, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Matesanz","sequence":"additional","affiliation":[{"name":"Laboratory and Clinical Analysis Department, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reyes","family":"Gim\u00e9nez","sequence":"additional","affiliation":[{"name":"Laboratory and Clinical Analysis Department, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Almudena","family":"Gal\u00e1n","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"},{"name":"Laboratory and Clinical Analysis Department, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Sanz","sequence":"additional","affiliation":[{"name":"Hematology and Hemotherapy Unit, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"},{"name":"Biomedical Research Foundation, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5444-8076","authenticated-orcid":false,"given":"Elena","family":"Sebasti\u00e1n","sequence":"additional","affiliation":[{"name":"Hematology and Hemotherapy Unit, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"},{"name":"Biomedical Research Foundation, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes\u00fas","family":"Gonz\u00e1lez de Pablo","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"de la Cruz","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"},{"name":"Laboratory and Clinical Analysis Department, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0332-6973","authenticated-orcid":false,"given":"Manuel","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Laboratory and Clinical Analysis Department, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"},{"name":"Pediatric Onco-Hematology Department, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"},{"name":"Health Research Institute at Hospital de La Princesa (IIS-Princesa), 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6852-1860","authenticated-orcid":false,"given":"Juli\u00e1n","family":"Sevilla","sequence":"additional","affiliation":[{"name":"Hematology and Hemotherapy Unit, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"},{"name":"Biomedical Research Foundation, Hospital Infantil Universitario Ni\u00f1o Jes\u00fas, 28009 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/ijlh.13179","article-title":"Diagnostic evaluation and considerations in hypocellular bone marrow failure\u2014A focus on genomics","volume":"42","author":"Fox","year":"2020","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/j.jmoldx.2022.09.009","article-title":"Clinical Validation and Diagnostic Utility of Optical Genome Mapping for Enhanced Cytogenomic Analysis of Hematological Neoplasms","volume":"24","author":"Sahajpal","year":"2022","journal-title":"J. Mol. Diagn."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/j.ajhg.2021.05.012","article-title":"Optical genome mapping enables constitutional chromosomal aberration detection","volume":"108","author":"Mantere","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1002\/ajh.26587","article-title":"Optical genome mapping for structural variation analysis in hematologic malignancies","volume":"97","author":"Smith","year":"2022","journal-title":"Am. J. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dremsek, P., Schwarz, T., Weil, B., Malashka, A., Laccone, F., and Neesen, J. (2021). Optical genome mapping in routine human genetic diagnostics\u2014Its advantages and limitations. Genes, 12.","DOI":"10.3390\/genes12121958"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Vieler, L.M., Nilius-Eliliwi, V., Schroers, R., Vangala, D.B., Nguyen, H.P., and Gerding, W.M. (2023). Optical Genome Mapping Reveals and Characterizes Recurrent Aberrations and New Fusion Genes in Adult ALL. Genes, 14.","DOI":"10.3390\/genes14030686"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Valkama, A., Vorimo, S., Kumpula, T.A., R\u00e4s\u00e4nen, H., Savolainen, E.R., Pylk\u00e4s, K., and Mantere, T. (2023). Optical Genome Mapping as an Alternative to FISH-Based Cytogenetic Assessment in Chronic Lymphocytic Leukemia. Cancers, 15.","DOI":"10.3390\/cancers15041294"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1038\/s41375-022-01652-8","article-title":"High-resolution structural variant profiling of myelodysplastic syndromes by optical genome mapping uncovers cryptic aberrations of prognostic and therapeutic significance","volume":"36","author":"Yang","year":"2022","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gao, H., Xu, H., Wang, C., Cui, L., Huang, X., Li, W., Yue, Z., Tian, S., Zhao, X., and Xue, T. (2023). Optical Genome Mapping for Comprehensive Assessment of Chromosomal Aberrations and Discovery of New Fusion Genes in Pediatric B-Acute Lymphoblastic Leukemia. Cancers, 15.","DOI":"10.3390\/cancers15010035"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1038\/s41375-019-0378-z","article-title":"European recommendations and quality assurance for cytogenomic analysis of haematological neoplasms","volume":"33","author":"Rack","year":"2019","journal-title":"Leukemia"},{"key":"ref_12","unstructured":"Espinet, B., Blanco, M.L., Costa, D., Cuatrecasas, E., and Ruiz-Xivill\u00e9, N. (2021). An\u00e1lisis Citogen\u00f3micos Aplicados a Neoplasias Hematol\u00f3gicas: Recomendaciones Preanal\u00edticas, Anal\u00edticas y Postanal\u00edticas [Cytogenomic Analysis Applied to Hematologic Neoplasms: Pre-Analytic, Analytic and Post-Analytic Recommendations], Sociedad Espa\u00f1ola de Hematolog\u00eda y Hemoterapia. [1st ed.]."},{"key":"ref_13","unstructured":"Woessner, S., and Florensa, L. (2006). La Citologia \u00d3ptica en el Diagn\u00f3stico Hematol\u00f3gico [Optical Cytology in Hematologic Diagnosis], Acci\u00f3n M\u00e9dica. [5th ed.]."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.stem.2023.01.006","article-title":"Clonal hematopoiesis driven by chromosome 1q\/MDM4 trisomy defines a canonical route toward leukemia in Fanconi anemia","volume":"30","author":"Sebert","year":"2023","journal-title":"Cell Stem Cell"},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1182\/asheducation-2011.1.84","article-title":"Classification of Childhood Aplastic Anemia and Myelodysplastic Syndrome","volume":"2011","author":"Niemeyer","year":"2011","journal-title":"Hematology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"151459","DOI":"10.1016\/j.anndiagpath.2019.151459","article-title":"Clinical impact of dysplastic changes in acquired aplastic anemia: A systematic study of bone marrow biopsies in children and adults","volume":"45","author":"Marchesi","year":"2020","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1007\/s12185-014-1674-z","article-title":"Cytogenetics and clinical features of pediatric myelodysplastic syndrome in Japan","volume":"100","author":"Moriwaki","year":"2014","journal-title":"Int. J. Hematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s00428-022-03447-9","article-title":"The International Consensus Classification (ICC) of hematologic neoplasms with germline predisposition, pediatric myelodysplastic syndrome, and juvenile myelomonocytic leukemia","volume":"482","author":"Rudelius","year":"2023","journal-title":"Virchows Arch."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e8442769","DOI":"10.1097\/01.HS9.0000973700.84427.69","article-title":"PB1708: Characterization of global cytogenomics features in childhood acute lymphoblastic leukemia by optical genome mapping","volume":"7","author":"Sanchez","year":"2023","journal-title":"Hemasphere"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1002\/ijc.33942","article-title":"Optical genome mapping reveals additional prognostic information compared to conventional cytogenetics in AML\/MDS patients","volume":"150","author":"Gerding","year":"2022","journal-title":"Int. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/s41408-022-00718-1","article-title":"Optical genome mapping refines cytogenetic diagnostics, prognostic stratification and provides new molecular insights in adult MDS\/AML patients","volume":"12","author":"Balducci","year":"2022","journal-title":"Blood Cancer J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/s41375-022-01763-2","article-title":"Optical Genome Mapping in MDS and AML as tool for structural variant profiling\u2014Comment and data update on Yang et al.: \u201cHigh-resolution structural variant profiling of myelodysplastic syndromes by optical genome mapping uncovers cryptic aberrations of prognostic and therapeutic significance\u201d","volume":"37","author":"Vangala","year":"2023","journal-title":"Leukemia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3000","DOI":"10.3324\/haematol.2021.279332","article-title":"A novel classification of hematologic conditions in patients with Fanconi anemia","volume":"106","author":"Behrens","year":"2021","journal-title":"Haematologica"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Nilius-Eliliwi, V., Gerding, W.M., Schroers, R., Nguyen, H.P., and Vangala, D.B. (2023). Optical Genome Mapping for Cytogenetic Diagnostics in AML. Cancers, 15.","DOI":"10.3390\/cancers15061684"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/5\/559\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:34:40Z","timestamp":1760106880000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/5\/559"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,27]]},"references-count":25,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["genes15050559"],"URL":"https:\/\/doi.org\/10.3390\/genes15050559","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,27]]}}}