{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T22:11:19Z","timestamp":1777414279057,"version":"3.51.4"},"reference-count":47,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"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>Somatic and epigenetic alterations contribute to myeloid leukemogenesis and play an important role in risk stratification and the optimization of treatment for myeloid malignancies. The significance of rare genetic alterations, such B-cell lymphoma-6 corepressor (BCOR) and B-cell lymphoma-6 corepressor-like protein 1 (BCORL1) mutations, in pediatric acute myeloid leukemias (AML) and myelodysplastic syndrome (MDS) is unknown. We present a case series of pediatric and adolescent patients, with de novo AML, harboring BCOR\/BCORL1 mutations. Studies involving larger cohorts of patients are needed to further elucidate the role of BCOR\/BCORL1 mutations in pediatric AML and MDS.<\/jats:p>","DOI":"10.3390\/cancers17152443","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T10:49:17Z","timestamp":1753267757000},"page":"2443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["BCOR, BCORL1, and BCL6 Mutations in Pediatric Leukemias"],"prefix":"10.3390","volume":"17","author":[{"given":"Thomas C.","family":"Fisher-Heath","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Indiana University School of Medicine, Riley Children\u2019s Health Indiana University Health, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7891-3625","authenticated-orcid":false,"given":"Aastha","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Indiana University School of Medicine, Riley Children\u2019s Health Indiana University Health, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark S.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Indiana University School of Medicine, Riley Children\u2019s Health Indiana University Health, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Indiana University School of Medicine, Riley Children\u2019s Health Indiana University Health, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5778-3200","authenticated-orcid":false,"given":"Sandeep","family":"Batra","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Indiana University School of Medicine, Riley Children\u2019s Health Indiana University Health, Indianapolis, IN 46202, USA"},{"name":"Indiana University Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.1182\/blood-2012-11-469619","article-title":"BCOR and BCORL1 mutations in myelodysplastic syndromes and related disorders","volume":"122","author":"Damm","year":"2013","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1158\/0008-5472.CAN-24-0132","article-title":"Comprehensive Genetic Profiling Reveals Frequent Alterations of Driver Genes on the X Chromosome in Extranodal NK\/T-cell Lymphoma","volume":"84","author":"Ito","year":"2024","journal-title":"Cancer Res."},{"key":"ref_3","first-page":"1779","article-title":"Genetic landscape and clinical outcomes of patients with BCOR mutated myeloid neoplasms","volume":"109","author":"Baranwal","year":"2024","journal-title":"Haematologica"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e194","DOI":"10.3324\/haematol.2014.117796","article-title":"BCOR and BCORL1 mutations in pediatric acute myeloid leukemia","volume":"100","author":"Hermkens","year":"2015","journal-title":"Haematologica"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Eckardt, J.-N., Stasik, S., Kramer, M., R\u00f6llig, C., Kr\u00e4mer, A., Scholl, S., Hochhaus, A., Crysandt, M., Br\u00fcmmendorf, T.H., and Naumann, R. (2021). Loss-of-Function Mutations of BCOR Are an Independent Marker of Adverse Outcomes in Intensively Treated Patients with Acute Myeloid Leukemia. Cancers, 13.","DOI":"10.3390\/cancers13092095"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1182\/blood.2021010958","article-title":"BCOR gene alterations in hematologic diseases","volume":"138","author":"Sportoletti","year":"2021","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Umeda, M., Liu, Y.-C., Karol, S.E., and Klco, J.M. (Haematologica, 2025). Novel classification system and high-risk categories of pediatric acute myeloid leukemia, Haematologica, ahead of print.","DOI":"10.3324\/haematol.2024.285644"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6880","DOI":"10.1128\/MCB.00630-06","article-title":"Polycomb group and SCF ubiquitin ligases are found in a novel BCOR complex that is recruited to BCL6 targets","volume":"26","author":"Gearhart","year":"2006","journal-title":"Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kaito, S., and Iwama, A. (2020). Pathogenic Impacts of Dysregulated Polycomb Repressive Complex Function in Hematological Malignancies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010074"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1158\/1541-7786.MCR-22-0567","article-title":"B-cell Lymphoma 6 (BCL6): From Master Regulator of Humoral Immunity to Oncogenic Driver in Pediatric Cancers","volume":"20","author":"McLachlan","year":"2022","journal-title":"Mol. Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1182\/blood-2018-01-827964","article-title":"Bcor insufficiency promotes initiation and progression of myelodysplastic syndrome","volume":"132","author":"Tara","year":"2018","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bouligny, I.M., Maher, K.R., and Grant, S. (2023). Secondary-Type Mutations in Acute Myeloid Leukemia: Updates from ELN 2022. Cancers, 15.","DOI":"10.3390\/cancers15133292"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2901","DOI":"10.1084\/jem.20170167","article-title":"Internal deletion of BCOR reveals a tumor suppressor function for BCOR in T lymphocyte malignancies","volume":"214","author":"Tanaka","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1038\/s41375-020-01075-3","article-title":"Bcor deficiency perturbs erythro-megakaryopoiesis and cooperates with Dnmt3a loss in acute erythroid leukemia onset in mice","volume":"35","author":"Sportoletti","year":"2021","journal-title":"Leukemia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1182\/blood.2018864173","article-title":"Engineered Bcor mutations lead to acute leukemia of progenitor B-1 lymphocyte origin in a sensitized background","volume":"133","author":"Yin","year":"2019","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1056\/NEJMra1904794","article-title":"Myelodysplastic Syndromes","volume":"383","author":"Cazzola","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1038\/s41375-020-0872-3","article-title":"Additional gene mutations may refine the 2017 European LeukemiaNet classification in adult patients with de novo acute myeloid leukemia aged <60 years","volume":"34","author":"Eisfeld","year":"2020","journal-title":"Leukemia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1080\/10428194.2024.2387730","article-title":"The clinical implications of BCOR mutations in a large cohort of acute myeloid leukemia patients: A 5-year single-center retrospective study","volume":"65","author":"Hu","year":"2024","journal-title":"Leuk. Lymphoma"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1007\/s00277-025-06346-6","article-title":"Impact of BCOR\/BCORL1 mutation on outcomes of allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia patients","volume":"104","author":"Zhou","year":"2025","journal-title":"Ann. Hematol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/nm.4439","article-title":"The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions","volume":"24","author":"Bolouri","year":"2018","journal-title":"Nat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.1200\/JCO.2009.25.6321","article-title":"Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98","volume":"28","author":"Reinhardt","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/MOP.0000000000000855","article-title":"Pediatric acute myeloid leukemia: Updates on biology, risk stratification, and therapy","volume":"32","author":"Elgarten","year":"2020","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s10555-020-09846-1","article-title":"The genomics of acute myeloid leukemia in children","volume":"39","author":"Conneely","year":"2020","journal-title":"Cancer Metastasis Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s12185-023-03533-x","article-title":"Comprehensive molecular understanding of pediatric acute myeloid leukemia","volume":"117","author":"Shiba","year":"2023","journal-title":"Int. J. Hematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3424","DOI":"10.1182\/blood-2016-01-695551","article-title":"Recurrent abnormalities can be used for risk group stratification in pediatric AMKL: A retrospective intergroup study","volume":"127","author":"Masetti","year":"2016","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1002\/cam4.5026","article-title":"Mutational landscape and clinical outcome of pediatric acute myeloid leukemia with 11q23\/KMT2A rearrangements","volume":"12","author":"Yuen","year":"2023","journal-title":"Cancer Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1111\/bjh.18354","article-title":"Development and validation of a prognostic scoring model to risk stratify childhood acute myeloid leukaemia","volume":"198","author":"Li","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Aparicio-P\u00e9rez, C., de la Torre, E.P., Sanchez-Garcia, J., Mart\u00edn-Calvo, C., Mart\u00ednez-Losada, C., Casa\u00f1o-Sanchez, J., Serrano-L\u00f3pez, J., and Serrano, J. (2023). Evolving Risk Classifications in AML in a Real-Life Scenario: After Changes upon Changes, Is It More and More Adverse?. Cancers, 15.","DOI":"10.3390\/cancers15051425"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1002\/gcc.22542","article-title":"Usefulness of BCOR gene mutation as a prognostic factor in acute myeloid leukemia with intermediate cytogenetic prognosis","volume":"57","author":"Terada","year":"2018","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"835","DOI":"10.2217\/epi-2018-0195","article-title":"BCOR involvement in cancer","volume":"11","author":"Astolfi","year":"2019","journal-title":"Epigenomics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1186\/s13148-021-01157-8","article-title":"Dynamics of epigenetic regulator gene BCOR mutation and response predictive value for hypomethylating agents in patients with myelodysplastic syndrome","volume":"13","author":"Li","year":"2021","journal-title":"Clin. Epigenet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5914","DOI":"10.1182\/blood-2011-05-356204","article-title":"Somatic mutations in the transcriptional corepressor gene BCORL1 in adult acute myelogenous leukemia","volume":"118","author":"Li","year":"2011","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1080\/10428194.2018.1543885","article-title":"BCOR and BCORL1 mutations in myelodysplastic syndromes (MDS): Clonal architecture and impact on outcomes","volume":"60","author":"Abuhadra","year":"2019","journal-title":"Leuk. Lymphoma"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.3324\/haematol.2016.160192","article-title":"Exome sequencing identifies recurrent BCOR alterations and the absence of KLF2, TNFAIP3 and MYD88 mutations in splenic diffuse red pulp small B-cell lymphoma","volume":"102","author":"Jallades","year":"2017","journal-title":"Haematologica"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"672","DOI":"10.3324\/haematol.2015.141796","article-title":"Wilms tumor 1 mutations in the pathogenesis of acute myeloid leukemia","volume":"101","author":"Rampal","year":"2016","journal-title":"Haematologica"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/s41588-023-01640-3","article-title":"A new genomic framework to categorize pediatric acute myeloid leukemia","volume":"56","author":"Umeda","year":"2024","journal-title":"Nat. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1182\/blood.2020010477","article-title":"Targeting intracellular WT1 in AML with a novel RMF-peptide-MHC-specific T-cell bispecific antibody","volume":"138","author":"Augsberger","year":"2021","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Aydin, S., Schmitz, J., Dellacasa, C.M., Dogliotti, I., Giaccone, L., and Busca, A. (2024). WT1 Expression Is Associated with Poor Overall Survival after Azacytidine and DLI in a Cohort of Adult AML and MDS Patients. Cancers, 16.","DOI":"10.3390\/cancers16173070"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1080\/10428194.2024.2441855","article-title":"Molecular, clinical, and prognostic implications of RAS pathway alterations in adult acute myeloid leukemia","volume":"66","author":"Zhang","year":"2025","journal-title":"Leuk. Lymphoma"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41408-024-01054-2","article-title":"RAS mutations in myeloid malignancies: Revisiting old questions with novel insights and therapeutic perspectives","volume":"14","author":"Alawieh","year":"2024","journal-title":"Blood Cancer J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1182\/bloodadvances.2023011165","article-title":"Genomic landscape of patients with germline RUNX1 variants and familial platelet disorder with myeloid malignancy","volume":"8","author":"Yu","year":"2024","journal-title":"Blood Adv."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1182\/blood.2019001745","article-title":"BCL6 maintains survival and self-renewal of primary human acute myeloid leukemia cells","volume":"137","author":"Kawabata","year":"2021","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zhang, L., Wu, M., Guo, W., Zhu, S., Li, S., Lv, S., Li, Y., Liu, L., Xing, Y., and Chen, H. (2023). A small molecule BCL6 inhibitor as chemosensitizers in acute myeloid leukemia. Biomed. Pharmacother., 166.","DOI":"10.1016\/j.biopha.2023.115358"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"116789","DOI":"10.1016\/j.ejmech.2024.116789","article-title":"Discovery of novel BCL6-Targeting PROTACs with effective antitumor activities against DLBCL in vitro and in vivo","volume":"277","author":"Mi","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1182\/blood-2007-04-087734","article-title":"Constitutively activated STAT3 promotes cell proliferation and survival in the activated B-cell subtype of diffuse large B-cell lymphomas","volume":"111","author":"Ding","year":"2008","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1182\/blood.2023023644","article-title":"Epigenetic regulation of noncanonical menin targets modulates menin inhibitor response in acute myeloid leukemia","volume":"144","author":"Zhou","year":"2024","journal-title":"Blood"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/15\/2443\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:14:33Z","timestamp":1760033673000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/15\/2443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,23]]},"references-count":47,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["cancers17152443"],"URL":"https:\/\/doi.org\/10.3390\/cancers17152443","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,23]]}}}