{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T04:27:22Z","timestamp":1787113642809,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"16","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":["Cancers"],"abstract":"<jats:p>Background: Accurate identification of pediatric B-cell acute lymphoblastic leukemia (B-ALL) patients at increased risk of relapse remains a major clinical challenge, as relapse occurs in 10\u201320% of cases, including patients initially classified as low- or intermediate-risk. This study aimed to identify clinical, genomic, and measurable residual disease (MRD) related predictors of relapse in pediatric B-ALL. Methods: 51 pediatric patients with B-ALL were included and followed for a median of 30.5 months (IQR, 16\u201345.5). Patients were stratified according to relapse status. At diagnosis, all cases underwent comprehensive genomic characterization based on the 2022 WHO and ICC classifications, including SNP-array analysis to identify copy number alterations (CNA) involving recurrent B-ALL genes (IKZF1, CDKN2A\/B, PAX5, ETV6, BTG1, EBF1, ERG, RB1, and PAR1) and to determine IKZF1plus status. Clinical variables, including white blood cell count, cytogenetic risk, and MRD assessed by flow cytometry at day 15, day 33, and at the end of induction, were analyzed. Kaplan\u2013Meier and Firth-penalized Cox regression analyses were performed to identify independent predictors of relapse. Results: 86.3% of patients were classified according to the 2022 WHO\/ICC classifications, with high hyperdiploidy being the most frequent subtype. During follow-up, 11 patients relapsed. Relapse was significantly associated with high cytogenetic risk (p = 0.007) and showed a trend toward association with an adverse CNA profile (p = 0.075). Patients with &gt;25% bone marrow blasts at day 15 (p &lt; 0.001) and those with positive MRD at the end of induction (p = 0.017) had a significantly higher risk of relapse. In multivariable analysis, high genetic risk and positive end-of-induction MRD remained independent predictors of relapse, with hazard ratios (HRs) of 9.31 (95% CI, 1.55\u201356.1), p = 0.010, and 10.9 (95% CI, 2.39\u201349.9), p = 0.002, respectively. Conclusions: An integrated diagnostic strategy including SNP-array provides a high diagnostic yield. High-risk cytogenetic abnormalities and positive end-of-induction MRD are independent predictors of relapse in pediatric B-ALL. Their combined assessment at diagnosis and early treatment may improve risk stratification and may support personalized therapeutic approaches.<\/jats:p>","DOI":"10.3390\/cancers18162633","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T15:48:36Z","timestamp":1786722516000},"page":"2633","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pediatric B-Cell Acute Lymphoblastic Leukemia: Comprehensive Genomic Characterization Including SNP-Array and Analysis of Relapse Risk"],"prefix":"10.3390","volume":"18","author":[{"given":"Concepci\u00f3n","family":"Prats-Mart\u00edn","sequence":"first","affiliation":[{"name":"Department of Hematology, Hospital Universitario Virgen del Roc\u00edo, Instituto de Biomedicina de Sevilla (IBIS\/CSIC\/CIBERONC), Universidad de Sevilla, Avda. Manuel Siurot sn., CP 41013 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"P\u00e9rez Ortega","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Virgen del Roc\u00edo, Instituto de Biomedicina de Sevilla (IBIS\/CSIC\/CIBERONC), Universidad de Sevilla, Avda. Manuel Siurot sn., CP 41013 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4972-917X","authenticated-orcid":false,"given":"\u00c1gueda","family":"Molinos Quintana","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Virgen del Roc\u00edo, Instituto de Biomedicina de Sevilla (IBIS\/CSIC\/CIBERONC), Universidad de Sevilla, Avda. Manuel Siurot sn., CP 41013 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4796-6470","authenticated-orcid":false,"given":"Jordi","family":"Ribera","sequence":"additional","affiliation":[{"name":"Josep Carreras Leukaemia Research Institute (IJC), ICO-Hospital Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Chiclana Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Virgen del Roc\u00edo, Instituto de Biomedicina de Sevilla (IBIS\/CSIC\/CIBERONC), Universidad de Sevilla, Avda. Manuel Siurot sn., CP 41013 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7487-3793","authenticated-orcid":false,"given":"Teresa","family":"Caballero-Vel\u00e1zquez","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Virgen del Roc\u00edo, Instituto de Biomedicina de Sevilla (IBIS\/CSIC\/CIBERONC), Universidad de Sevilla, Avda. Manuel Siurot sn., CP 41013 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estrella","family":"Carrillo Cruz","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Virgen del Roc\u00edo, Instituto de Biomedicina de Sevilla (IBIS\/CSIC\/CIBERONC), Universidad de Sevilla, Avda. Manuel Siurot sn., CP 41013 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5079-3420","authenticated-orcid":false,"given":"Henry Antonio","family":"Andrade-Ruiz","sequence":"additional","affiliation":[{"name":"Methodological and Statistical Support Unit, Fundaci\u00f3n para la Gesti\u00f3n de la Investigaci\u00f3n en Salud de Sevilla (FISEVI), 41013 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Paz","family":"Garrastazul S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Puerta del Mar, 11009 C\u00e1diz, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Dolores","family":"Madrigal Toscano","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Virgen Macarena, 41009 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Sol\u00e9 Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Juan Ram\u00f3n Jim\u00e9nez, 21005 Huelva, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"G\u00f3mez Rosa","sequence":"additional","affiliation":[{"name":"UGC Hematolog\u00eda y Hemoterapia, Hospital Universitario Virgen de Valme, 41014 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3616-6101","authenticated-orcid":false,"given":"Jos\u00e9 Antonio","family":"P\u00e9rez-Sim\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Virgen del Roc\u00edo, Instituto de Biomedicina de Sevilla (IBIS\/CSIC\/CIBERONC), Universidad de Sevilla, Avda. 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Incidence and Time Trends of Childhood Hematological Neoplasms: A 36-Year Population-Based Study in the Southern European Context, 1983\u20132018. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1197850"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S1470-2045(17)30186-9","article-title":"International Incidence of Childhood Cancer, 2001\u20132010: A Population-Based Registry Study","volume":"18","author":"Colombet","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e142","DOI":"10.1016\/S1470-2045(19)30031-2","article-title":"Comparative Features and Outcomes Between Paediatric T-Cell and B-Cell Acute Lymphoblastic Leukaemia","volume":"20","author":"Teachey","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"103571","DOI":"10.1016\/j.eclinm.2025.103571","article-title":"Global Incidence of Childhood Cancer by Subtype in 2022: A Population-Based Registry Study","volume":"89","author":"Wang","year":"2025","journal-title":"EClinicalMedicine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1038\/s41375-022-01540-1","article-title":"Temporal Changes in Incidence of Relapse and Outcome After Relapse of Childhood Acute Lymphoblastic Leukemia over Three Decades; A Nordic Population-Based Cohort Study","volume":"36","author":"Jensen","year":"2022","journal-title":"Leukemia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1586\/17474086.2015.978281","article-title":"Risk Factors for Relapse in Childhood Acute Lymphoblastic Leukemia: Prediction and Prevention","volume":"8","author":"Ceppi","year":"2015","journal-title":"Expert Rev. Hematol."},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s00428-022-03448-8","article-title":"International Consensus Classification of Acute Lymphoblastic Leukemia\/Lymphoma","volume":"482","author":"Duffield","year":"2023","journal-title":"Virchows Arch."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1182\/bloodadvances.2018025718","article-title":"Validation of the United Kingdom Copy-Number Alteration Classifier in 3239 Children with B-Cell Precursor ALL","volume":"3","author":"Hamadeh","year":"2019","journal-title":"Blood Adv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1038\/s41375-025-02758-5","article-title":"DUX4-Rearranged B-ALL: Deciphering a Biological and Clinical Conundrum","volume":"39","author":"Bakewell","year":"2025","journal-title":"Leukemia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1093\/ajcp\/aqx005","article-title":"CRLF2-Positive B-Cell Acute Lymphoblastic Leukemia in Adult Patients: A Single-Institution Experience","volume":"147","author":"Konoplev","year":"2017","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kruse, A., Abdel-Azim, N., Kim, H.N., Ruan, Y., Phan, V., Ogana, H., Wang, W., Lee, R., Gang, E.J., and Khazal, S. (2020). Minimal Residual Disease Detection in Acute Lymphoblastic Leukemia. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031054"},{"key":"ref_13","unstructured":"Badell Serra, I. (2014). Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children Aged 1\u201319 Years: LAL\/SEHOP-PETHEMA 2013 Therapeutic Recommendations, Version 2.0, SEHOP\/PETHEMA."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1200\/JCO.19.00261","article-title":"Outcome of Infants Younger than 1 Year with Acute Lymphoblastic Leukemia Treated with the Interfant-06 Protocol: Results from an International Phase III Randomized Study","volume":"37","author":"Pieters","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_15","unstructured":"ALLTogether Consortium (2023). ALLTogether1: A Treatment Study Protocol of the ALLTogether Consortium for Children and Young Adults (0\u201345 Years of Age) with Newly Diagnosed Acute Lymphoblastic Leukaemia, ClinicalTrials.gov Identifier: NCT04307576."},{"key":"ref_16","unstructured":"EuroFlow Consortium (2026, July 29). Composition and Technical Info of EuroFlow Panels for Hematological Malignancies, Version 1.12. Available online: https:\/\/euroflow.org\/protocols\/."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1182\/blood-2016-07-726307","article-title":"Standardized Flow Cytometry for Highly Sensitive MRD Measurements in B-Cell Acute Lymphoblastic Leukemia","volume":"129","author":"Theunissen","year":"2017","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/bjh.17992","article-title":"Flow Cytometric Minimal Residual Disease Assessment in B-Cell Precursor Acute Lymphoblastic Leukaemia Patients Treated with CD19-Targeted Therapies\u2014A EuroFlow Study","volume":"197","author":"Verbeek","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_19","unstructured":"Hastings, R.J., Chrometska, M., and Haase, D. (2024). ISCN 2024: An International System for Human Cytogenomic Nomenclature, S. Karger AG."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e53","DOI":"10.1097\/HS9.0000000000000053","article-title":"Advances in B-Cell Precursor Acute Lymphoblastic Leukemia Genomics","volume":"2","author":"Schwab","year":"2018","journal-title":"HemaSphere"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1038\/s41436-019-0545-7","article-title":"Technical Laboratory Standards for Interpretation and Reporting of Acquired Copy-Number Abnormalities and Copy-Neutral Loss of Heterozygosity in Neoplastic Disorders: A Joint Consensus Recommendation from the American College of Medical Genetics and Genomics (ACMG) and the Cancer Genomics Consortium (CGC)","volume":"21","author":"Mikhail","year":"2019","journal-title":"Genet. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1200\/JCO.2017.74.3617","article-title":"IKZF1plus Defines a New Minimal Residual Disease-Dependent Very-Poor Prognostic Profile in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia","volume":"36","author":"Stanulla","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/leu.2013.277","article-title":"An Intragenic ERG Deletion Is a Marker of an Oncogenic Subtype of B-Cell Precursor Acute Lymphoblastic Leukemia with a Favorable Outcome Despite Frequent IKZF1 Deletions","volume":"28","author":"Clappier","year":"2014","journal-title":"Leukemia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jmoldx.2016.10.002","article-title":"Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists","volume":"19","author":"Li","year":"2017","journal-title":"J. Mol. Diagn."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/j.jmoldx.2022.08.001","article-title":"Sequential Approach to Improve the Molecular Classification of Childhood Acute Lymphoblastic Leukemia","volume":"24","author":"Yu","year":"2022","journal-title":"J. Mol. Diagn."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 Revision to the World Health Organization Classification of Myeloid Neoplasms and Acute Leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1007\/s00277-024-06151-7","article-title":"How to Combine Multiple Tools for the Genetic Diagnosis Work-Up of Pediatric B-Cell Acute Lymphoblastic Leukemia","volume":"104","author":"Balsalobre","year":"2025","journal-title":"Ann. Hematol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1182\/bloodadvances.2022009179","article-title":"Classification and Genetics of Pediatric B-Other Acute Lymphoblastic Leukemia by Targeted RNA Sequencing","volume":"7","author":"Migita","year":"2023","journal-title":"Blood Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.3324\/haematol.2018.204974","article-title":"Genomic Landscape of Pediatric B-Other Acute Lymphoblastic Leukemia in a Consecutive European Cohort","volume":"104","author":"Zaliova","year":"2019","journal-title":"Haematologica"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1182\/blood-2014-03-562918","article-title":"A Novel Integrated Cytogenetic and Genomic Classification Refines Risk Stratification in Pediatric Acute Lymphoblastic Leukemia","volume":"124","author":"Moorman","year":"2014","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1002\/gcc.20502","article-title":"Mutations of FLT3, NRAS, KRAS, and PTPN11 Are Frequent and Possibly Mutually Exclusive in High Hyperdiploid Childhood Acute Lymphoblastic Leukemia","volume":"47","author":"Paulsson","year":"2008","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e782","DOI":"10.1097\/HS9.0000000000000782","article-title":"Clinical and Prognostic Impact of Copy Number Alterations and Associated Risk Profiles in a Cohort of Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia Cases Treated Under ICiCLe Protocol","volume":"6","author":"Gupta","year":"2022","journal-title":"HemaSphere"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhang, H., Wang, Y., Ouyang, J., Yang, J., Zhang, L., Wang, X., Liu, J., Zhou, X., Zheng, S., and Han, L. (2020). Genetic Mutational Analysis of Pediatric Acute Lymphoblastic Leukemia from a Single Center in China Using Exon Sequencing. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-6709-7"},{"key":"ref_34","first-page":"3046","article-title":"Multiclonal Complexity of Pediatric Acute Lymphoblastic Leukemia and the Prognostic Relevance of Subclonal Mutations","volume":"106","author":"Toft","year":"2021","journal-title":"Haematologica"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e923271","DOI":"10.12659\/MSM.923271","article-title":"Risk Factors for Relapse of Childhood B Cell Acute Lymphoblastic Leukemia","volume":"26","author":"Zhang","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Navas-Acosta, J., Hidalgo-G\u00f3mez, G., Mart\u00ednez-Laperche, C., de Toledo, J.S., S\u00e1nchez-Silos, R., Men\u00e9ndez, P., Antillon-Klussmann, F., Mar\u00edn, M., Balsalobre, P., and Bueno, C. (2024). Preferential Genetic Pathways Lead to Relapses in Adult B-Cell Acute Lymphoblastic Leukemia. Cancers, 16.","DOI":"10.3390\/cancers16244200"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/leu.2015.199","article-title":"Prognostic Value of Rare IKZF1 Deletion in Childhood B-Cell Precursor Acute Lymphoblastic Leukemia: An International Collaborative Study","volume":"30","author":"Boer","year":"2016","journal-title":"Leukemia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.jtct.2025.01.003","article-title":"Refining Risk Stratification for B-Cell Precursor Adult Acute Lymphoblastic Leukemia Treated with a Pediatric-Inspired Regimen by Combining IKZF1 Deletion and Minimal Residual Disease","volume":"4","author":"Deng","year":"2025","journal-title":"Transplant. Cell. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3512","DOI":"10.1182\/blood-2011-11-394221","article-title":"Outcome Modeling with CRLF2, IKZF1, JAK, and Minimal Residual Disease in Pediatric Acute Lymphoblastic Leukemia: A Children\u2019s Oncology Group Study","volume":"119","author":"Chen","year":"2012","journal-title":"Blood"},{"key":"ref_40","unstructured":"Verbeek, M.W.C., van der Sluijs-Gelling, A.J., de Bie, M., de Haas, V., de Groot-Kruseman, H.A., de Jong, A., de Ligt, J., de Pagter, A.P.J., de Rooij, A.E., and van der Velden, V.H.J. (2024). The Evolving Landscape of Flow Cytometric Minimal Residual Disease Monitoring in B-Cell Precursor Acute Lymphoblastic Leukemia. Int. J. Mol. Sci., 25."},{"key":"ref_41","unstructured":"Spanish Society of Pediatric Hematology and Oncology (SEHOP), and Programa Espa\u00f1ol de Tratamientos en Hematolog\u00eda (PETHEMA) (2026, July 29). LAL-SEHOP-PETHEMA 2013: Protocolo para el Tratamiento de la Leucemia Linfobl\u00e1stica aguda Infantil. Madrid, Spain, 2014. Available online: https:\/\/www.sehh.es\/images\/stories\/recursos\/2014\/documentos\/guias\/LAL_SEHOP_PETHEMA_2013.pdf."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lejman, M., Ku\u015b, J., Cha\u0142as, A., Pastorczak, A., M\u0142ynarski, W., and Zawitkowska, J. (2022). Genetic Biomarkers and Their Clinical Implications in B-Cell Acute Lymphoblastic Leukemia in Children. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052755"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100","DOI":"10.3325\/cmj.2025.66.100","article-title":"Disease Characteristics and Outcomes of Croatian Pediatric Patients with Acute Lymphoblastic Leukemia: Pretreatment Immunophenotypic Predictors of High Bone Marrow Minimal Residual Disease on Day 15 of Treatment","volume":"66","author":"Bonevski","year":"2025","journal-title":"Croat. Med. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1182\/blood-2016-03-704973","article-title":"Integration of Genetic and Clinical Risk Factors Improves Prognostication in Relapsed Childhood B-Cell Precursor Acute Lymphoblastic Leukemia","volume":"128","author":"Irving","year":"2016","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e828","DOI":"10.1016\/S2352-3026(21)00304-5","article-title":"Defining Low-Risk High Hyperdiploidy in Patients with Paediatric Acute Lymphoblastic Leukaemia: A Retrospective Analysis of Data from the UKALL97\/99 and UKALL2003 Clinical Trials","volume":"8","author":"Enshaei","year":"2021","journal-title":"Lancet Haematol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/ng.3301","article-title":"The Genomic Landscape of High Hyperdiploid Childhood Acute Lymphoblastic Leukemia","volume":"47","author":"Paulsson","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhang, J., Wang, Y., Ouyang, J., Yang, J., Zhang, L., Wang, X., Liu, J., Zhou, X., Zheng, S., and Han, L. (2022). Clinical and Genetic Characteristics of IKZF1 Mutation in Chinese Children with B-Cell Acute Lymphoblastic Leukemia. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.822832"},{"key":"ref_48","first-page":"13","article-title":"TBL1XR1 in Physiological and Pathological States","volume":"3","author":"Li","year":"2015","journal-title":"Am. J. Clin. Exp. Urol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1182\/blood.V79.9.2384.2384","article-title":"Isochromosomes in Childhood Acute Lymphoblastic Leukemia: A Collaborative Study of 83 Cases","volume":"79","author":"Pui","year":"1992","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/s41588-018-0315-5","article-title":"PAX5-Driven Subtypes of B-Progenitor Acute Lymphoblastic Leukemia","volume":"51","author":"Gu","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4413","DOI":"10.1007\/s00277-024-05667-2","article-title":"Prognostic Significance of CRLF2 in Patients with Acute Lymphoblastic Leukemia: A Meta-Analysis and Systematic Review","volume":"103","author":"Meng","year":"2024","journal-title":"Ann. Hematol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1038\/leu.2016.365","article-title":"Genomic and Transcriptional Landscape of P2RY8-CRLF2-Positive Childhood Acute Lymphoblastic Leukemia","volume":"31","author":"Vesely","year":"2017","journal-title":"Leukemia"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/leu.2013.223","article-title":"VPREB1 Deletions Occur Independent of Lambda Light Chain Rearrangement in Childhood Acute Lymphoblastic Leukemia","volume":"28","author":"Mangum","year":"2014","journal-title":"Leukemia"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.3324\/haematol.11239","article-title":"Incidence and Outcome of TCF3-PBX1-Positive Acute Lymphoblastic Leukemia in Austrian Children","volume":"92","author":"Kager","year":"2007","journal-title":"Haematologica"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1038\/leu.2009.42","article-title":"Increased Risk for CNS Relapse in Pre-B Cell Leukemia with the t(1;19)\/TCF3-PBX1","volume":"23","author":"Jeha","year":"2009","journal-title":"Leukemia"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1111\/bjh.17844","article-title":"Prognostic Heterogeneity of Adult B-Cell Precursor Acute Lymphoblastic Leukaemia Patients with t(1;19)(q23;p13)\/TCF3-PBX1 Treated with Measurable Residual Disease-Oriented Protocols","volume":"196","author":"Ribera","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hidalgo, M., Cabrera-Sojo, M., Jim\u00e9nez, R., P\u00e9rez-Hurtado, J.M., Morales, T., Ceballos, M.A., and P\u00e9rez-Sim\u00f3n, J.A. (2025). Intrachromosomal Amplification of Chromosome 21 (iAMP21) Impacts Event-Free Survival but Not Overall Survival Among Pediatric Patients with Acute Lymphoblastic Leukemia: A Single-Center Experience Using an Asparaginase-Intensified Spanish Regimen. Hemato, 6.","DOI":"10.3390\/hemato6030019"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Molina, O., Vinyoles, M., Ruiz-Xancho, M., Soler, G., Camps, J., Ribera, J.M., Fuster, J.L., Men\u00e9ndez, P., and Comeza\u00f1a-Fern\u00e1ndez, J.A. (2021). Near-Haploidy and Low-Hypodiploidy in B-Cell Acute Lymphoblastic Leukemia: When Less Is Too Much. 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