{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T18:04:06Z","timestamp":1776708246392,"version":"3.51.2"},"reference-count":79,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>High hyperdiploidy (HHD) is the most common cytogenetic abnormality in childhood B-cell acute lymphoblastic leukemia (B-ALL) and is a pivotal finding for prognosis evaluation and treatment stratification. Karyotyping is considered the gold standard for detecting HHD; however, cytogenetic cultures sometimes fail. The DNA index (DI) analysis by flow cytometry (FCM) is a quick and simple approach to estimating HHD without the need for cultures. The aim of this study was to assess the diagnostic performance of DI for detecting HHD in pediatric patients with B-ALL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A cross-sectional study was conducted on 210 pediatric patients with B-ALL at Instituto Nacional de Salud del Ni\u00f1o San Borja (INSNSB) in Peru between 2017 and 2021. The receiver operating characteristic (ROC) curve was analyzed using karyotype results as the reference standard to determine the optimal DI cut-off value for HHD. The main diagnostic performance indicators were subsequently described. Immunophenotypic characteristics associated with HHD were also explored using a generalized linear model (GLM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A 25.2% (n\u2009=\u200953\/210) rate of failed karyotypes was observed. DI\u2009\u2265\u20091.10 showed a sensitivity of 96.6% (95% CI: 93.7\u201399.4%), specificity of 89.8% (95% CI: 85.1\u201394.6%), positive predictive value of 68.3% (95% CI: 61.0\u201375.6%), negative predictive value of 99.1% (95% CI: 97.7\u2013100.0%), and AUC of 0.947 (95% CI: 0.914\u20130.980). The overall concordance between DI and karyotype was 91.1% (n\u2009=\u2009143\/157), with a Kappa index 0.75 (95% CI: 0.62\u20130.87). Blast size (PR\u2009=\u20094.8, 95% CI: 2.7\u20138.5) and CD123 expression (95% CI: 1.9\u201373) were associated with HHD (p\u2009&lt;\u20090.001 and p\u2009&lt;\u20090.009, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>DI has a high diagnostic performance and is helpful as a complementary method to karyotyping for detecting HHD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0347201","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T17:33:56Z","timestamp":1776706436000},"page":"e0347201","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic performance of DNA index for detection of high hyperdiploidy in childhood B-cell acute lymphoblastic leukemia"],"prefix":"10.1371","volume":"21","author":[{"given":"C\u00e9sar","family":"Rivera-Orcoapaza","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1665-2332","authenticated-orcid":true,"given":"Jaime","family":"Rosales-Rimache","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"issue":"36","key":"pone.0347201.ref001","doi-asserted-by":"crossref","first-page":"5579","DOI":"10.1200\/JCO.23.01286","article-title":"Advancing diagnostics and therapy to reach universal cure in childhood ALL","volume":"41","author":"R Pieters","year":"2023","journal-title":"J Clin Oncol"},{"issue":"7","key":"pone.0347201.ref002","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":"JAE Irving","year":"2016","journal-title":"Blood"},{"issue":"7","key":"pone.0347201.ref003","doi-asserted-by":"crossref","DOI":"10.1016\/j.clml.2019.09.603","article-title":"Study of cytogenetic alterations and association with prognostic factors in indian children with B-lineage acute lymphoblastic leukemia","volume":"20","author":"M Agarwal","year":"2020","journal-title":"Clin Lymphoma Myeloma Leuk"},{"issue":"8","key":"pone.0347201.ref004","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1002\/gcc.20671","article-title":"High hyperdiploid childhood acute lymphoblastic leukemia","volume":"48","author":"K Paulsson","year":"2009","journal-title":"Genes Chromosomes Cancer"},{"key":"pone.0347201.ref005","volume-title":"World Health Organization classification of tumours of haematopoietic and lymphoid tissues","author":"SH Swerdlow","year":"2017","edition":"4"},{"issue":"3","key":"pone.0347201.ref006","doi-asserted-by":"crossref","first-page":"416","DOI":"10.17843\/rpmesp.2018.353.2947","article-title":"Sobrevida global y libre de enfermedad en una cohorte peruana de pacientes con leucemia linfobl\u00e1stica aguda","volume":"35","author":"S Castro-Arechaga","year":"2018","journal-title":"Rev Peru Med Exp Salud Publica"},{"issue":"6","key":"pone.0347201.ref007","doi-asserted-by":"crossref","DOI":"10.1002\/pbc.26327","article-title":"High hyperdiploid acute lymphoblastic leukemia (ALL)-A 25-year population-based survey of the Austrian ALL-BFM (Berlin-Frankfurt-M\u00fcnster) Study Group","volume":"64","author":"B Reism\u00fcller","year":"2017","journal-title":"Pediatr Blood Cancer"},{"issue":"6","key":"pone.0347201.ref008","doi-asserted-by":"crossref","first-page":"413","DOI":"10.3343\/alm.2014.34.6.413","article-title":"Cancer cytogenetics: methodology revisited","volume":"34","author":"TSK Wan","year":"2014","journal-title":"Ann Lab Med"},{"issue":"5","key":"pone.0347201.ref009","doi-asserted-by":"crossref","first-page":"396","DOI":"10.5114\/polp.2018.80689","article-title":"Significance of numerical chromosome abnormalities in children with acute leukaemias detected by flow cytometry","volume":"93","author":"M Pierzyna-\u015awita\u0142a","year":"2018","journal-title":"Pediatr Pol"},{"issue":"4","key":"pone.0347201.ref010","doi-asserted-by":"crossref","first-page":"263","DOI":"10.4103\/sajc.sajc_13_18","article-title":"Impact of cytogenetics on outcomes in pediatric acute lymphoblastic leukemia","volume":"7","author":"R Chennamaneni","year":"2018","journal-title":"South Asian J Cancer"},{"key":"pone.0347201.ref011","article-title":"Genetics, cytogenetic testing and conventional karyotype","author":"E Ozkan","year":"2024","journal-title":"StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing"},{"key":"pone.0347201.ref012","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-12-811710-1.00012-4","article-title":"Chapter 14 - Animal tissue culture principles and applications.","volume-title":"Animal biotechnology","author":"A Verma","year":"2020"},{"issue":"21","key":"pone.0347201.ref013","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.4155\/bio-2021-0071","article-title":"A flow cytometric journey into cell cycle analysis","volume":"13","author":"A Nair","year":"2021","journal-title":"Bioanalysis"},{"key":"pone.0347201.ref014","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-0716-3738-8","volume-title":"Flow cytometry protocols","author":"TS Hawley","year":"2024","edition":"5"},{"key":"pone.0347201.ref015","doi-asserted-by":"crossref","DOI":"10.1002\/cpim.36","article-title":"Analysis of cellular DNA content by flow cytometry","volume":"119","author":"Z Darzynkiewicz","year":"2017","journal-title":"Curr Protoc Immunol"},{"issue":"3","key":"pone.0347201.ref016","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1155\/1998\/712042","article-title":"Flow cytometric DNA index and karyotype in childhood lymphoblastic leukemia","volume":"17","author":"E Forestier","year":"1998","journal-title":"Anal Cell Pathol"},{"issue":"05","key":"pone.0347201.ref017","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1055\/s-0043-1776046","article-title":"Flow cytometric ploidy analysis in acute lymphoblastic leukemia and plasma cell myeloma","volume":"44","author":"K Bommannan","year":"2023","journal-title":"Indian J Med Paediatr Oncol"},{"key":"pone.0347201.ref018","unstructured":"Instituto Nacional de Salud del Ni\u00f1o San Borja. Gu\u00eda de pr\u00e1ctica cl\u00ednica de leucemia linfobl\u00e1stica aguda; 2016 [cited 2020 Apr 23]. Available from:http:\/\/www.insnsb.gob.pe\/guias-de-practica-clinicas\/"},{"issue":"10","key":"pone.0347201.ref019","doi-asserted-by":"crossref","first-page":"8764","DOI":"10.3390\/ijms24108764","article-title":"Overview on aneuploidy in childhood B-cell acute lymphoblastic leukemia","volume":"24","author":"K Panuciak","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"12","key":"pone.0347201.ref020","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1038\/s41375-022-01720-z","article-title":"Hyperdiploidy: the longest known, most prevalent, and most enigmatic form of acute lymphoblastic leukemia in children","volume":"36","author":"OA Haas","year":"2022","journal-title":"Leukemia"},{"issue":"9","key":"pone.0347201.ref021","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1038\/leu.2012.120","article-title":"EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes","volume":"26","author":"JJM van Dongen","year":"2012","journal-title":"Leukemia"},{"issue":"10","key":"pone.0347201.ref022","first-page":"1783","article-title":"Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL)","volume":"9","author":"MC Bene","year":"1995","journal-title":"Leukemia"},{"issue":"3","key":"pone.0347201.ref023","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/j.1751-553X.2009.01189.x","article-title":"DNA Index in childhood acute lymphoblastic leukaemia: a karyotypic method to validate the flow cytometric measurement","volume":"32","author":"P Rachieru-Sourisseau","year":"2010","journal-title":"Int J Lab Hematol"},{"issue":"2","key":"pone.0347201.ref024","doi-asserted-by":"crossref","first-page":"45","DOI":"10.4103\/joah.joah_14_18","article-title":"Discrepancies between DNA index by flow cytometry and cytogenetic studies in childhood B-lymphoblastic leukemia","volume":"9","author":"N Almozain","year":"2018","journal-title":"J Appl Hematol"},{"issue":"17","key":"pone.0347201.ref025","doi-asserted-by":"crossref","first-page":"7917","DOI":"10.7314\/APJCP.2015.16.17.7917","article-title":"DNA ploidy and S-phase fraction analysis in paediatric B-cell acute lymphoblastic leukemia cases: a tertiary care centre experience","volume":"16","author":"BK Kumar","year":"2015","journal-title":"Asian Pac J Cancer Prev"},{"issue":"3","key":"pone.0347201.ref026","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/cyto.a.22821","article-title":"A bright and colorful future for DNA cell cycle analysis","volume":"89","author":"CM Yuan","year":"2016","journal-title":"Cytometry A"},{"key":"pone.0347201.ref027","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.cancergen.2019.07.009","article-title":"Masked hypodiploidy: hypodiploid acute lymphoblastic leukemia (ALL) mimicking hyperdiploid ALL in children: a report from the Children\u2019s Oncology Group","volume":"238","author":"AJ Carroll","year":"2019","journal-title":"Cancer Genet"},{"issue":"5","key":"pone.0347201.ref028","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1002\/cyto.b.21765","article-title":"FxCycle\u2122 based ploidy correlates with cytogenetic ploidy in B-cell acute lymphoblastic leukemia and is able to detect the aneuploid minimal residual disease clone","volume":"96","author":"N Gupta","year":"2019","journal-title":"Cytometry B Clin Cytom"},{"issue":"3","key":"pone.0347201.ref029","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/cyto.a.22803","article-title":"A novel and easy FxCycle\u2122 violet based flow cytometric method for simultaneous assessment of DNA ploidy and six-color immunophenotyping","volume":"89","author":"P Tembhare","year":"2016","journal-title":"Cytometry A"},{"key":"pone.0347201.ref030","article-title":"Method for DNA ploidy analysis along with immunophenotyping for rare populations in a sample using FxCycle violet","volume":"80","author":"P Tembhare","year":"2017","journal-title":"Curr Protoc Cytom"},{"issue":"1","key":"pone.0347201.ref031","first-page":"34","article-title":"Flow cytometric DNA ploidy analysis in haemato-lymphoid neoplasms: an analysis of 132 cases","volume":"16","author":"N Gupta","year":"2022","journal-title":"Int J Hematol Oncol Stem Cell Res"},{"key":"pone.0347201.ref032","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/978-1-4419-6199-0_9","article-title":"Analysis of cellular DNA content by flow and laser scanning cytometry","volume":"676","author":"Z Darzynkiewicz","year":"2010","journal-title":"Adv Exp Med Biol"},{"key":"pone.0347201.ref033","article-title":"Critical aspects in analysis of cellular DNA content","author":"Z Darzynkiewicz","year":"2011","journal-title":"Curr Protoc Cytom"},{"key":"pone.0347201.ref034","article-title":"Nucleic acid probes","author":"M Poot","year":"2004","journal-title":"Curr Protoc Cytom"},{"issue":"7","key":"pone.0347201.ref035","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/cyto.990110702","article-title":"A review of techniques and results obtained in one laboratory by an integrated system of methods designed for routine clinical flow cytometric DNA analysis","volume":"11","author":"LL Vindel\u00f8v","year":"1990","journal-title":"Cytometry"},{"issue":"5","key":"pone.0347201.ref036","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/cyto.990140507","article-title":"Consensus review of the clinical utility of DNA flow cytometry in neoplastic hematopathology","volume":"14","author":"RE Duque","year":"1993","journal-title":"Cytometry"},{"key":"pone.0347201.ref037","article-title":"Quality assurance and quality control in clinical cytogenetics","author":"MS Watson","year":"2007","journal-title":"Curr Protoc Hum Genet"},{"issue":"2","key":"pone.0347201.ref038","article-title":"Pre-analytical parameters associated with unsuccessful karyotyping in myeloid neoplasm: a study of 421 samples","volume":"52","author":"MFM Santos","year":"2019","journal-title":"Braz J Med Biol Res"},{"key":"pone.0347201.ref039","article-title":"Immunophenotypic characterization of cytogenetic subgroups in Egyptian pediatric patients with B-cell acute lymphoblastic leukemia","author":"S Adnan Awad","year":"2016","journal-title":"Clin Lymphoma Myeloma Leuk"},{"issue":"1","key":"pone.0347201.ref040","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13039-022-00635-9","article-title":"Cytogenetic culture failure and its causes in hematological disorders; a single centre perspective","volume":"16","author":"S Javed","year":"2023","journal-title":"Mol Cytogenet"},{"issue":"9","key":"pone.0347201.ref041","first-page":"1","article-title":"The fundamentals to minimize the culture failure in hematological malignancies","volume":"7","author":"S Martinovic","year":"2020","journal-title":"Open Access Libr J"},{"issue":"8","key":"pone.0347201.ref042","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":"KA Rack","year":"2019","journal-title":"Leukemia"},{"issue":"1","key":"pone.0347201.ref043","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/cyto.b.21523","article-title":"Simultaneous use of multiplex ligation-dependent probe amplification assay and flow cytometric DNA ploidy analysis in patients with acute leukemia","volume":"94","author":"V Reyes-N\u00fa\u00f1ez","year":"2018","journal-title":"Cytometry B Clin Cytom"},{"issue":"1","key":"pone.0347201.ref044","doi-asserted-by":"crossref","first-page":"11501","DOI":"10.1038\/s41598-020-68311-9","article-title":"MLPA and DNA index improve the molecular diagnosis of childhood B-cell acute lymphoblastic leukemia","volume":"10","author":"C-H Yu","year":"2020","journal-title":"Sci Rep"},{"key":"pone.0347201.ref045","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.leukres.2017.05.022","article-title":"Aneuploidy identification in pre-B acute lymphoblastic leukemia patients at diagnosis by Multiplex Ligation-dependent Probe Amplification (MLPA)","volume":"59","author":"A V\u00e1zquez-Reyes","year":"2017","journal-title":"Leuk Res"},{"issue":"10","key":"pone.0347201.ref046","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/gcc.22971","article-title":"Optical genome mapping, a promising alternative to gold standard cytogenetic approaches in a series of acute lymphoblastic leukemias","volume":"60","author":"V Lestringant","year":"2021","journal-title":"Genes Chromosomes Cancer"},{"issue":"1","key":"pone.0347201.ref047","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0165-4608(95)00027-5","article-title":"Hyperdiploid acute myeloid leukemia. Relationship between blast size and karyotype demonstrated by fluorescence in situ hybridization","volume":"83","author":"YL Kwong","year":"1995","journal-title":"Cancer Genet Cytogenet"},{"issue":"4","key":"pone.0347201.ref048","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1111\/ijlh.13436","article-title":"Blast size-specific flowcytometric ploidy assessment using FxCycleTM Violet dye and its correlation with conventional cytogenetic ploidy in pediatric precursor B-lineage acute lymphoblastic leukemia patients","volume":"43","author":"K Bommannan","year":"2021","journal-title":"Int J Lab Hematol"},{"issue":"7","key":"pone.0347201.ref049","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.3324\/haematol.2008.000299","article-title":"Overexpression of CD123 correlates with the hyperdiploid genotype in acute lymphoblastic leukemia","volume":"94","author":"M Djokic","year":"2009","journal-title":"Haematologica"},{"issue":"1","key":"pone.0347201.ref050","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1038\/s41467-023-37356-5","article-title":"Clonal origin and development of high hyperdiploidy in childhood acute lymphoblastic leukaemia","volume":"14","author":"EL Woodward","year":"2023","journal-title":"Nat Commun"},{"issue":"3","key":"pone.0347201.ref051","first-page":"1","article-title":"Caracterizaci\u00f3n biol\u00f3gica del marcador CD66c y su importancia cl\u00ednica en la leucemia linfoide aguda","volume":"34","author":"S Cruz Rubio","year":"2018","journal-title":"Rev Cuba Hematol Inmunol Hemoter"},{"issue":"1","key":"pone.0347201.ref052","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.leukres.2013.10.008","article-title":"Significance of CD66c expression in childhood acute lymphoblastic leukemia","volume":"38","author":"N Kiyokawa","year":"2014","journal-title":"Leuk Res"},{"issue":"4","key":"pone.0347201.ref053","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1182\/blood-2016-10-743765","article-title":"Near-haploid and low-hypodiploid acute lymphoblastic leukemia: two distinct subtypes with consistently poor prognosis","volume":"129","author":"S Safavi","year":"2017","journal-title":"Blood"},{"issue":"4","key":"pone.0347201.ref054","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1182\/blood-2006-07-038299","article-title":"Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia","volume":"110","author":"JB Nachman","year":"2007","journal-title":"Blood"},{"issue":"2","key":"pone.0347201.ref055","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/bjh.15770","article-title":"Aneuploidy in children with relapsed B-cell precursor acute lymphoblastic leukaemia: clinical importance of detecting a hypodiploid origin of relapse","volume":"185","author":"S Groeneveld-Krentz","year":"2019","journal-title":"Br J Haematol"},{"issue":"11","key":"pone.0347201.ref056","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1038\/s41375-024-02395-4","article-title":"Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children\u2019s Oncology Group study","volume":"38","author":"SR Rheingold","year":"2024","journal-title":"Leukemia"},{"issue":"1","key":"pone.0347201.ref057","doi-asserted-by":"crossref","first-page":"32","DOI":"10.3390\/cancers14010032","article-title":"Near-haploidy and low-hypodiploidy in B-cell acute lymphoblastic leukemia: when less is too much","volume":"14","author":"O Molina","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"3","key":"pone.0347201.ref058","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/cyto.b.22063","article-title":"Detecting hypodiploidy with endoreduplication and masked hypodiploidy in B-cell acute lymphoblastic leukemia using multicolor flow cytometry","volume":"102","author":"A Chaturvedi","year":"2022","journal-title":"Cytometry B Clin Cytom"},{"issue":"4","key":"pone.0347201.ref059","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1007\/s12288-021-01409-w","article-title":"A systematic cytogenetic strategy to identify masked hypodiploidy in precursor B acute lymphoblastic leukemia in low resource settings","volume":"37","author":"T Gupta","year":"2021","journal-title":"Indian J Hematol Blood Transfus"},{"key":"pone.0347201.ref060","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1186\/s12935-019-1013-9","article-title":"Clinical-biological characteristics and treatment outcomes of pediatric pro-B ALL patients enrolled in BCH-2003 and CCLG-2008 protocol: a study of 121 Chinese children","volume":"19","author":"C Gao","year":"2019","journal-title":"Cancer Cell Int"},{"issue":"7","key":"pone.0347201.ref061","doi-asserted-by":"crossref","DOI":"10.1001\/jamaoncol.2017.0580","article-title":"Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: a meta-analysis","volume":"3","author":"DA Berry","year":"2017","journal-title":"JAMA Oncol"},{"key":"pone.0347201.ref062","doi-asserted-by":"crossref","first-page":"923","DOI":"10.3389\/fonc.2020.00923","article-title":"Day 15 and day 33 minimal residual disease assessment for acute lymphoblastic leukemia patients treated according to the BFM ALL IC 2009 protocol: single-center experience of 133 cases","volume":"10","author":"L-E Radu","year":"2020","journal-title":"Front Oncol"},{"issue":"2","key":"pone.0347201.ref063","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/cyto.b.21769","article-title":"Early (day 15 post diagnosis) peripheral blood assessment of measurable residual disease in flow cytometry is a strong predictor of outcome in childhood B-lineage lymphoblastic leukemia","volume":"96","author":"M Loosveld","year":"2019","journal-title":"Cytometry B Clin Cytom"},{"issue":"35","key":"pone.0347201.ref064","doi-asserted-by":"crossref","first-page":"5422","DOI":"10.1200\/JCO.23.00880","article-title":"Prognostic and pharmacotypic heterogeneity of hyperdiploidy in childhood ALL","volume":"41","author":"SHR Lee","year":"2023","journal-title":"J Clin Oncol"},{"issue":"1","key":"pone.0347201.ref065","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1186\/s12885-021-08545-6","article-title":"DNA index as prognostic factor in childhood acute lymphoblastic leukemia in the COG-TARGET database","volume":"21","author":"K-Y Qiu","year":"2021","journal-title":"BMC Cancer"},{"issue":"1","key":"pone.0347201.ref066","first-page":"33","article-title":"DNA-Ploidy - a prognostic factor of Acute Lymphoblastic Leukemia (ALL) in childhood","volume":"23","author":"O Basu","year":"2009","journal-title":"Asian J Exp Sci"},{"issue":"13","key":"pone.0347201.ref067","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1182\/blood-2012-06-437681","article-title":"Hyperdiploidy with 58-66 chromosomes in childhood B-acute lymphoblastic leukemia is highly curable: 58951 CLG-EORTC results","volume":"121","author":"N Dastugue","year":"2013","journal-title":"Blood"},{"issue":"9","key":"pone.0347201.ref068","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1002\/gcc.22374","article-title":"Slower early response to treatment and distinct expression profile of childhood high hyperdiploid acute lymphoblastic leukaemia with DNA index <\u20091.16","volume":"55","author":"M Zaliova","year":"2016","journal-title":"Genes Chromosomes Cancer"},{"issue":"4","key":"pone.0347201.ref069","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.bjhh.2015.03.009","article-title":"Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival","volume":"37","author":"DW Lustosa de Sousa","year":"2015","journal-title":"Rev Bras Hematol Hemoter"},{"issue":"2","key":"pone.0347201.ref070","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1200\/JCO.2007.12.3927","article-title":"Long-term results of the AIEOP-ALL-95 trial for childhood acute lymphoblastic leukemia: insight on the prognostic value of DNA index in the framework of Berlin-Frankfurt-Muenster based chemotherapy","volume":"26","author":"M Aric\u00f2","year":"2008","journal-title":"J Clin Oncol"},{"issue":"2","key":"pone.0347201.ref071","first-page":"149","article-title":"Advances and issues in flow cytometric detection of immunophenotypic changes and genomic rearrangements in acute pediatric leukemia","volume":"3","author":"XM Wang","year":"2014","journal-title":"Transl Pediatr"},{"issue":"3","key":"pone.0347201.ref072","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1097\/01.mph.0000210064.80828.3e","article-title":"Flow cytometric DNA index, G-band karyotyping, and comparative genomic hybridization in detection of high hyperdiploidy in childhood acute lymphoblastic leukemia","volume":"28","author":"U Nygaard","year":"2006","journal-title":"J Pediatr Hematol Oncol"},{"key":"pone.0347201.ref073","doi-asserted-by":"crossref","DOI":"10.1016\/j.jdent.2018.04.022","article-title":"Fuzzy gold standards: Approaches to handling an imperfect reference standard","volume":"74","author":"T Walsh","year":"2018","journal-title":"J Dent"},{"issue":"10","key":"pone.0347201.ref074","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0223832","article-title":"Diagnostic test evaluation methodology: a systematic review of methods employed to evaluate diagnostic tests in the absence of gold standard - An update","volume":"14","author":"CM Umemneku Chikere","year":"2019","journal-title":"PLoS One"},{"issue":"50","key":"pone.0347201.ref075","article-title":"Evaluation of diagnostic tests when there is no gold standard. A review of methods","volume":"11","author":"AWS Rutjes","year":"2007","journal-title":"Health Technol Assess"},{"issue":"50","key":"pone.0347201.ref076","doi-asserted-by":"crossref","first-page":"21719","DOI":"10.1073\/pnas.1006981107","article-title":"Genetic landscape of high hyperdiploid childhood acute lymphoblastic leukemia","volume":"107","author":"K Paulsson","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"pone.0347201.ref077","doi-asserted-by":"crossref","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":"A Enshaei","year":"2021","journal-title":"Lancet Haematol"},{"issue":"3","key":"pone.0347201.ref078","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1002\/pbc.22628","article-title":"Frequencies of ETV6-RUNX1 fusion and hyperdiploidy in pediatric acute lymphoblastic leukemia are lower in far east than west","volume":"55","author":"D-C Liang","year":"2010","journal-title":"Pediatr Blood Cancer"},{"issue":"3","key":"pone.0347201.ref079","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1001\/jamaoncol.2021.6826","article-title":"Association of genetic ancestry with the molecular subtypes and prognosis of childhood acute lymphoblastic leukemia","volume":"8","author":"SHR Lee","year":"2022","journal-title":"JAMA Oncol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0347201","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T17:34:10Z","timestamp":1776706450000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0347201"}},"subtitle":[],"editor":[{"given":"Arthur J.","family":"Lustig","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":79,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0347201","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]}}}