{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T18:20:14Z","timestamp":1779301214497,"version":"3.51.4"},"reference-count":37,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T00:00:00Z","timestamp":1753747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Lublin","award":["DS411"],"award-info":[{"award-number":["DS411"]}]},{"name":"Medical University of Lublin","award":["GI13"],"award-info":[{"award-number":["GI13"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: In childhood acute lymphoblastic leukemia (ALL), in addition to classical chromosomal abnormalities, loss of heterozygosity (LOH), including copy-neutral LOH, is also observed. While LOH has been described in the literature, its clinical relevance in pediatric ALL remains unclear. The aim of this study is to identify and analyze patterns of LOH, assess their frequency, and evaluate their association with clinical characteristics and early treatment response during the induction phase of the ALL protocol. Methods: The study included 853 pediatric ALL patients, of whom 120 had B-ALL LOH+ and 58 had T-ALL LOH+. LOH was analyzed using CytoScan HD SNP microarrays. Patients were stratified using multiple correspondence analysis (MCA) and hierarchical clustering on principal components (HCPC), which identified three genetically and clinically distinct clusters. Results: In B-ALL, two clusters with extensive LOH\u2014particularly involving chromosome 9\u2014were associated with poor prognosis and suboptimal response to therapy. In contrast, Cluster 2, characterized by CDKN2A duplication and rare LOH, showed a favorable clinical course. In T-ALL, Cluster 1 had LOH in CDKN2A but favorable outcomes; Cluster 2 exhibited biallelic CDKN2A deletion and aggressive disease; Cluster 3 lacked CDKN2A alterations and showed a genetically stable profile. LOH was common on chromosomes not typically affected by trisomy and rare on those gained. Conclusions: Our study indicates that LOH profiling can positively influence patient stratification by identifying high-risk subgroups, inform prognosis by highlighting unfavorable genetic alterations, and help predict poor treatment response in specific clinical profiles.<\/jats:p>","DOI":"10.3390\/cancers17152500","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T12:39:29Z","timestamp":1753792769000},"page":"2500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Loss of Heterozygosity in Pediatric Acute Lymphoblastic Leukemia and Its Prognostic Impact: A Retrospective Study"],"prefix":"10.3390","volume":"17","author":[{"given":"Borys","family":"Styka","sequence":"first","affiliation":[{"name":"Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9728-5281","authenticated-orcid":false,"given":"Gabriela","family":"R\u0119ka","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Ozyga\u0142a","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7116-6783","authenticated-orcid":false,"given":"Mariola","family":"Janiszewska","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics and Statistics with e-Health Lab, Medical University of Lublin, 20-059 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Stelmach","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulina","family":"Skowera","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuzanna","family":"Urba\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Genetic Predisposition to Cancer, Medical University of Lodz, 92-216 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8760-0775","authenticated-orcid":false,"given":"Monika","family":"Lejman","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"ref_1","unstructured":"Puckett, Y., and Chan, O. (2023). Acute Lymphocytic Leukemia, StatPearls Publishing."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1182\/asheducation-2018.1.69","article-title":"Genomics of aggressive B-cell lymphoma","volume":"2018","author":"Rosenthal","year":"2018","journal-title":"Hematology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e577","DOI":"10.1038\/bcj.2017.53","article-title":"Acute lymphoblastic leukemia: A comprehensive review and 2017 update","volume":"7","author":"Terwilliger","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1159\/000337297","article-title":"Integrated analysis of gene copy number, copy neutral LOH, and microRNA profiles in adult acute lymphoblastic leukemia","volume":"136","author":"Ninomiya","year":"2012","journal-title":"Cytogenet. Genome Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zhang, X., and Sj\u00f6blom, T. (2021). Targeting Loss of Heterozygosity: A Novel Paradigm for Cancer Therapy. Pharmaceuticals, 14.","DOI":"10.3390\/ph14010057"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ryland, G.L., Doyle, M.A., Goode, D., Boyle, S.E., Choong, D.Y., Rowley, S.M., Li, J., Australian Ovarian Cancer Study Group, Bowtell, D.D., and Tothill, R.W. (2015). Loss of heterozygosity: What is it good for?. BMC Med. Genom., 8.","DOI":"10.1186\/s12920-015-0123-z"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1002\/gcc.22851","article-title":"Decreased copy-neutral loss of heterozygosity in African American colorectal cancers","volume":"59","author":"Augustus","year":"2020","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4962","DOI":"10.1158\/1078-0432.CCR-14-0353","article-title":"Excess of proximal microsatellite-stable colorectal cancer in African Americans from a multiethnic study","volume":"20","author":"Xicola","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/sj.leu.2402727","article-title":"Long-term study of the clinical significance of loss of heterozygosity in childhood acute lymphoblastic leukemia","volume":"17","author":"Takeuchi","year":"2003","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1182\/bloodadvances.2018016584","article-title":"Refining risk classification in childhood B acute lymphoblastic leukemia: Results of DFCI ALL Consortium Protocol 05-001","volume":"2","author":"Vrooman","year":"2018","journal-title":"Blood Adv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1054\/blre.2001.0150","article-title":"The detection and significance of chromosomal abnormalities in childhood acute lymphoblastic leukaemia","volume":"15","author":"Harrison","year":"2001","journal-title":"Blood Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S1470-2045(10)70066-8","article-title":"Prognostic effect of chromosomal abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: Results from the UK Medical Research Council ALL97\/99 randomised trial","volume":"11","author":"Moorman","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1056\/NEJM200012283432602","article-title":"Genomic aberrations and survival in chronic lymphocytic leukemia","volume":"343","author":"Stilgenbauer","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lejman, M., W\u0142odarczyk, M., Styka, B., Pastorczak, A., Zawitkowska, J., Taha, J., S\u0119dek, \u0141., Skonieczka, K., Braun, M., and Haus, O. (2020). Advantages and Limitations of SNP Array in the Molecular Characterization of Pediatric T-Cell Acute Lymphoblastic Leukemia. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01184"},{"key":"ref_15","unstructured":"(2025, July 28). A Randomized Trial of the I-BFM-SG for the Management of Childhood\u2014B Acute Lymphoblastic Leukemia. Available online: http:\/\/www.bialaczka.org\/wp-content\/uploads\/2016\/10\/ALLIC_BFM_2009.pdf."},{"key":"ref_16","unstructured":"(2025, July 28). Treatment Protocol for Children and Adolescents with Acute Lymphoblastic Leukemia\u2014AIEOP-BFM ALL, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03643276."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.cancergen.2018.07.005","article-title":"Assessing copy number abnormalities and copy-neutral loss-of-heterozygosity across the genome as best practice in diagnostic evaluation of acute myeloid leukemia: An evidence-based review from the cancer genomics consortium (CGC) myeloid neoplasms working group","volume":"228\u2013229","author":"Xu","year":"2018","journal-title":"Cancer Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6109","DOI":"10.1182\/blood-2011-12-397620","article-title":"Loss of heterozygosity in 7q myeloid disorders: Clinical associations and genomic pathogenesis","volume":"119","author":"Jerez","year":"2012","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1038\/sj.leu.2401069","article-title":"High-resolution allelotype analysis of childhood B-lineage acute lymphoblastic leukemia","volume":"12","author":"Duval","year":"1998","journal-title":"Leukemia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S0145-2126(97)00075-1","article-title":"Allelic loss in childhood acute lymphoblastic leukemia","volume":"21","author":"Baccichet","year":"1997","journal-title":"Leuk. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Risinskaya, N., Gladysheva, M., Abdulpatakhov, A., Chabaeva, Y., Surimova, V., Aleshina, O., Yushkova, A., Dubova, O., Kapranov, N., and Galtseva, I. (2023). DNA Copy Number Alterations and Copy Neutral Loss of Heterozygosity in Adult Ph-Negative Acute B-Lymphoblastic Leukemia: Focus on the Genes Involved. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242417602"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e31129","DOI":"10.1002\/pbc.31129","article-title":"The impact of comparative genomic hybridization\/single-nucleotide polymorphism microarray in risk stratification of pediatric acute lymphoblastic leukemia","volume":"71","author":"Gourmel","year":"2024","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ampatzidou, M., Papadhimitriou, S.I., Paisiou, A., Paterakis, G., Tzanoudaki, M., Papadakis, V., Florentin, L., and Polychronopoulou, S. (2023). The Prognostic Effect of CDKN2A\/2B Gene Deletions in Pediatric Acute Lymphoblastic Leukemia (ALL): Independent Prognostic Significance in BFM-Based Protocols. Diagnostics, 13.","DOI":"10.3390\/diagnostics13091589"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101463","DOI":"10.1016\/j.trim.2021.101463","article-title":"Pretransplant HLA mistyping in diagnostic sample of a T-ALL patient due to loss of heterozygosity in the major histocompatibility complex","volume":"69","author":"Shi","year":"2021","journal-title":"Transpl. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3869","DOI":"10.1182\/blood.V86.10.3869.bloodjournal86103869","article-title":"Loss of heterozygosity in the chromosomal region 12p12-13 is very common in childhood acute lymphoblastic leukemia and permits the precise localization of a tumor-suppressor gene distinct from p27KIP1","volume":"86","author":"Martin","year":"1995","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Risinskaya, N., Kozhevnikova, Y., Gavrilina, O., Chabaeva, J., Kotova, E., Yushkova, A., Isinova, G., Zarubina, K., Obukhova, T., and Kulikov, S. (2022). Loss of Heterozygosity in the Tumor DNA of De Novo Diagnosed Patients Is Associated with Poor Outcome for B-ALL but Not for T-ALL. Genes, 13.","DOI":"10.3390\/genes13030398"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1038\/s41375-019-0412-1","article-title":"SH2B3 inactivation through CN-LOH 12q is uniquely associated with B-cell precursor ALL with iAMP21 or other chromosome 21 gain","volume":"33","author":"Sinclair","year":"2019","journal-title":"Leukemia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1182\/blood-2008-07-166801","article-title":"A comprehensive analysis of the CDKN2A gene in childhood acute lymphoblastic leukemia reveals genomic deletion, copy number neutral loss of heterozygosity, and association with specific cytogenetic subgroups","volume":"113","author":"Sulong","year":"2009","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2832","DOI":"10.1182\/blood-2024-205213","article-title":"Recurrent molecular variants, clonal evolution and clinical relevance in T-cell lymphoblastic neoplasia comparing lymphoma and leukemia samples derived from children and adults","volume":"144","author":"Sandmann","year":"2024","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/nature05690","article-title":"Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia","volume":"446","author":"Mullighan","year":"2007","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Vijayakrishnan, J., Henrion, M., Moorman, A.V., Fiege, B., Kumar, R., Filho, M., Holroyd, A., Koehler, R., Thomsen, H., and Irving, J.A. (2015). The 9p21.3 risk of childhood acute lymphoblastic leukaemia is explained by a rare high-impact variant in CDKN2A. Sci. Rep., 5.","DOI":"10.1038\/srep15065"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1200\/JCO.2014.59.1636","article-title":"Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration","volume":"33","author":"Pui","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.3324\/haematol.2013.085175","article-title":"Genes commonly deleted in childhood B-cell precursor acute lymphoblastic leukemia: Association with cytogenetics and clinical features","volume":"98","author":"Schwab","year":"2013","journal-title":"Haematologica"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1080\/07853890.2018.1564359","article-title":"Prognostic significance of CDKN2A\/B deletions in acute lymphoblastic leukaemia: A meta-analysis","volume":"51","author":"Zhang","year":"2019","journal-title":"Ann. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1002\/ajh.26069","article-title":"CDKN2A deletions are associated with poor outcomes in 101 adults with T-cell acute lymphoblastic leukemia","volume":"96","author":"Wang","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s11864-020-00757-5","article-title":"Biology and Treatment Paradigms in T Cell Acute Lymphoblastic Leukemia in Older Adolescents and Adults","volume":"21","author":"Patel","year":"2020","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Gil, C., Ribera, J., Ribera, J.M., and Genesc\u00e0, E. (2021). The Yin and Yang-Like Clinical Implications of the CDKN2A\/ARF\/CDKN2B Gene Cluster in Acute Lymphoblastic Leukemia. Genes, 12.","DOI":"10.3390\/genes12010079"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/15\/2500\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:18:10Z","timestamp":1760033890000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/15\/2500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,29]]},"references-count":37,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["cancers17152500"],"URL":"https:\/\/doi.org\/10.3390\/cancers17152500","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,29]]}}}