{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:17:04Z","timestamp":1760239024287,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:00:00Z","timestamp":1600646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Consejer\u00eda de Educaci\u00f3n, Junta de Castilla y Le\u00f3n, Fondos FEDER","award":["SA085U16","SA271P18"],"award-info":[{"award-number":["SA085U16","SA271P18"]}]},{"name":"Regional Council of Castilla y Le\u00f3n SACYL","award":["GRS 2062\/A\/19","GRS 1847\/A\/18"],"award-info":[{"award-number":["GRS 2062\/A\/19","GRS 1847\/A\/18"]}]},{"name":"Proyectos de investigaci\u00f3n en Biomedicina, gesti\u00f3n sanitaria y atenci\u00f3n sociosanitaria del IBSAL","award":["IBY17\/00006"],"award-info":[{"award-number":["IBY17\/00006"]}]},{"DOI":"10.13039\/501100014139","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer","doi-asserted-by":"publisher","award":["CB16\/12\/00233"],"award-info":[{"award-number":["CB16\/12\/00233"]}],"id":[{"id":"10.13039\/501100014139","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Synthetic Lethality for Personalized Therapy-based Stratification In Acute Leukemia","award":["ERAPERMED2018-275"],"award-info":[{"award-number":["ERAPERMED2018-275"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["AC18\/00093"],"award-info":[{"award-number":["AC18\/00093"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002704","name":"Fundaci\u00f3n Cient\u00edfica Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","doi-asserted-by":"publisher","award":["Adri\u00e1n Monta\u00f1o"],"award-info":[{"award-number":["Adri\u00e1n Monta\u00f1o"]}],"id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: B-acute lymphoblastic leukemia (B-ALL) is a hematological neoplasm of the stem lymphoid cell of the B lineage, characterized by the presence of genetic alterations closely related to the course of the disease. The number of alterations identified in these patients grows as studies of the disease progress, but in clinical practice, the conventional techniques frequently used are only capable of detecting the most common alterations. However, techniques, such as next-generation sequencing (NGS), are being implemented to detect a wide spectrum of new alterations that also include point mutations. Methods: In this study, we designed and validated a comprehensive custom NGS panel to detect the main genetic alterations present in the disease in a single step. For this purpose, 75 B-ALL diagnosis samples from patients previously characterized by standard-of-care diagnostic techniques were sequenced. Results: The use of the custom NGS panel allowed the correct detection of the main genetic alterations present in B-ALL patients, including the presence of an aneuploid clone in 14 of the samples and some of the recurrent fusion genes in 35 of the samples. The panel was also able to successfully detect a number of secondary alterations, such as single nucleotide variants (SNVs) and copy number variations (CNVs) in 66 and 46 of the samples analyzed, respectively, allowing for further refinement of the stratification of patients. The custom NGS panel could also detect alterations with a high level of sensitivity and reproducibility when the findings obtained by NGS were compared with those obtained from other conventional techniques. Conclusions: The use of this custom NGS panel allows us to quickly and efficiently detect the main genetic alterations present in B-ALL patients in a single assay (SNVs and insertions\/deletions (INDELs), recurrent fusion genes, CNVs, aneuploidies, and single nucleotide polymorphisms (SNPs) associated with pharmacogenetics). The application of this panel would thus allow us to speed up and simplify the molecular diagnosis of patients, helping patient stratification and management.<\/jats:p>","DOI":"10.3390\/jpm10030137","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T08:18:01Z","timestamp":1600676281000},"page":"137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Comprehensive Custom NGS Panel Validation for the Improvement of the Stratification of B-Acute Lymphoblastic Leukemia Patients"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3178-6726","authenticated-orcid":false,"given":"Adri\u00e1n","family":"Monta\u00f1o","sequence":"first","affiliation":[{"name":"IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes\u00fas","family":"Hern\u00e1ndez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5205-8891","authenticated-orcid":false,"given":"Maribel","family":"Forero-Castro","sequence":"additional","affiliation":[{"name":"Escuela de Ciencias Biol\u00f3gicas (Grupo de investigaci\u00f3n GICBUPTC), Universidad Pedag\u00f3gica y Tecnol\u00f3gica de Colombia, Tunja 150003, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4787-3266","authenticated-orcid":false,"given":"Mar\u00eda","family":"Matorra-Miguel","sequence":"additional","affiliation":[{"name":"IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Lumbreras","sequence":"additional","affiliation":[{"name":"IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Miguel","sequence":"additional","affiliation":[{"name":"IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Santos","sequence":"additional","affiliation":[{"name":"IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Ram\u00edrez-Maldonado","sequence":"additional","affiliation":[{"name":"IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4881-9440","authenticated-orcid":false,"given":"Jos\u00e9 Lu\u00eds","family":"Fuster","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Oncohematolog\u00eda Pedi\u00e1trica, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB), 30120 Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"de Las Heras","sequence":"additional","affiliation":[{"name":"Departamento de Hematolog\u00eda\u2014Hospital Virgen Blanca, 24008 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfonso","family":"Garc\u00eda-de Coca","sequence":"additional","affiliation":[{"name":"Departamento de Hematolog\u00eda\u2014Hospital Cl\u00ednico de Valladolid, 47003 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Sierra","sequence":"additional","affiliation":[{"name":"Complejo Sanitario de Zamora, 49022 Zamora, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5185-2073","authenticated-orcid":false,"given":"Julio","family":"D\u00e1vila","sequence":"additional","affiliation":[{"name":"Departamento de Hematolog\u00eda\u2014Hospital Universitario de Salamanca, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignacio","family":"de la Fuente","sequence":"additional","affiliation":[{"name":"Departamento de Hematolog\u00eda\u2014Hospital Rio Hortega, 47012 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9739-5747","authenticated-orcid":false,"given":"Carmen","family":"Olivier","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Hemoterapia\u2014Complejo Sanitario de Segovia, 40002 Segovia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Olazabal","sequence":"additional","affiliation":[{"name":"Departamento de Hematolog\u00eda\u2014Hospital Universitario de Burgos, 09006 Burgos, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7908-0063","authenticated-orcid":false,"given":"Joaqu\u00edn","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Departamento de Hematolog\u00eda\u2014Hospital Universitario 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3190-063X","authenticated-orcid":false,"given":"Nerea","family":"Vega-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratorio de Hematolog\u00eda, Instituto de Investigaci\u00f3n, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Departamento de Hematolog\u00eda\u2014Hospital Universitario de Salamanca, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes\u00fas Mar\u00eda","family":"Hern\u00e1ndez-Rivas","sequence":"additional","affiliation":[{"name":"IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), 37007 Salamanca, Spain"},{"name":"Departamento de Hematolog\u00eda\u2014Hospital Universitario de Salamanca, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9781-4198","authenticated-orcid":false,"given":"Roc\u00edo","family":"Benito","sequence":"additional","affiliation":[{"name":"IBSAL, IBMCC, Universidad de Salamanca, CSIC, Centro de Investigaci\u00f3n del C\u00e1ncer (CIC), 37007 Salamanca, 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Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/sj.leu.2402883","article-title":"Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements","volume":"17","author":"Pui","year":"2003","journal-title":"Leukemia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/S0140-6736(19)33018-1","article-title":"Acute lymphoblastic leukaemia","volume":"395","author":"Malard","year":"2020","journal-title":"Lancet"},{"key":"ref_5","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_6","doi-asserted-by":"crossref","unstructured":"Stary, J., Zuna, J., and Zaliova, M. (2018). New biological and genetic classification and therapeutically relevant categories in childhood B-cell precursor acute lymphoblastic leukemia. F1000Research, 7.","DOI":"10.12688\/f1000research.16074.1"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s11899-016-0337-y","article-title":"Treatment of Childhood Acute Lymphoblastic Leukemia: Prognostic Factors and Clinical Advances","volume":"11","author":"Vrooman","year":"2016","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.1182\/blood-2015-02-580043","article-title":"Redefining ALL classification: Toward detecting high-risk ALL and implementing precision medicine","volume":"125","author":"Hunger","year":"2015","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1182\/blood.2019000813","article-title":"IKZF1 deletions in pediatric acute lymphoblastic leukemia: Still a poor prognostic marker?","volume":"135","author":"Stanulla","year":"2020","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1182\/blood.2019002220","article-title":"Therapy-induced mutations drive the genomic landscape of relapsed acute lymphoblastic leukemia","volume":"135","author":"Li","year":"2020","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4634","DOI":"10.1038\/s41598-019-41078-4","article-title":"Copy number alterations in B-cell development genes, drug resistance, and clinical outcome in pediatric B-cell precursor acute lymphoblastic leukemia","volume":"9","author":"Steeghs","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"4810","DOI":"10.1182\/blood-2009-05-223081","article-title":"BTG1 regulates glucocorticoid receptor autoinduction in acute lymphoblastic leukemia","volume":"115","author":"Kuiper","year":"2010","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/j.1365-2141.2010.08314.x","article-title":"Biology and Diagnosis Committee of International Berlin-Frankfurt-Munster study, g. Detection of prognostically relevant genetic abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: Recommendations from the Biology and Diagnosis Committee of the International Berlin-Frankfurt-Munster study group","volume":"151","author":"Harrison","year":"2010","journal-title":"Br. J. Haematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1038\/s41375-019-0378-z","article-title":"European recommendations and quality assurance for cytogenomic analysis of haematological neoplasms","volume":"33","author":"Rack","year":"2019","journal-title":"Leukemia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1016\/j.leukres.2010.02.031","article-title":"Prognostic classification of patients with acute lymphoblastic leukemia by using gene copy number profiles identified from array-based comparative genomic hybridization data","volume":"34","author":"Usvasalo","year":"2010","journal-title":"Leuk. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1053\/j.seminoncol.2008.04.007","article-title":"Cytogenetic, molecular genetic, and clinical characteristics of acute myeloid leukemia with a complex karyotype","volume":"35","author":"Mrozek","year":"2008","journal-title":"Semin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Coccaro, N., Anelli, L., Zagaria, A., Specchia, G., and Albano, F. (2019). Next-Generation Sequencing in Acute Lymphoblastic Leukemia. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20122929"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Rehm, H.L., Hynes, E., and Funke, B.H. (2016). The Changing Landscape of Molecular Diagnostic Testing: Implications for Academic Medical Centers. J. Pers. Med., 6.","DOI":"10.3390\/jpm6010008"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrg.2016.162","article-title":"Evolving health care through personal genomics","volume":"18","author":"Rehm","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"102033","DOI":"10.18632\/oncotarget.22116","article-title":"Development and validation of a targeted next generation DNA sequencing panel outperforming whole exome sequencing for the identification of clinically relevant genetic variants","volume":"8","author":"Miller","year":"2017","journal-title":"Oncotarget"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/gim.2017.119","article-title":"Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test","volume":"20","author":"Lionel","year":"2018","journal-title":"Genet. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1056\/NEJM199808273390907","article-title":"Acute lymphoblastic leukemia","volume":"339","author":"Pui","year":"1998","journal-title":"New Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Forero-Castro, M., Robledo, C., Benito, R., Abaigar, M., Africa Martin, A., Arefi, M., Fuster, J.L., de Las Heras, N., Rodriguez, J.N., and Quintero, J. (2016). Genome-Wide DNA Copy Number Analysis of Acute Lymphoblastic Leukemia Identifies New Genetic Markers Associated with Clinical Outcome. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148972"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Montano, A., Ordonez, J.L., Alonso-Perez, V., Hernandez-Sanchez, J., Santos, S., Gonzalez, T., Benito, R., Garcia-Tunon, I., and Hernandez-Rivas, J.M. (2020). ETV6\/RUNX1 Fusion Gene Abrogation Decreases the Oncogenicity of Tumour Cells in a Preclinical Model of Acute Lymphoblastic Leukaemia. Cells, 9.","DOI":"10.3390\/cells9010215"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: The human genomic variant search engine","volume":"35","author":"Kopanos","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3324\/haematol.2017.171132","article-title":"Introducing high-throughput sequencing into mainstream genetic diagnosis practice in inherited platelet disorders","volume":"103","author":"Bastida","year":"2018","journal-title":"Haematologica"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1093\/bioinformatics\/btv710","article-title":"Manta: Rapid detection of structural variants and indels for germline and cancer sequencing applications","volume":"32","author":"Chen","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/bjc.2017.152","article-title":"Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia","volume":"117","author":"Robledo","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1002\/gcc.20818","article-title":"Evaluation of multiplex ligation-dependent probe amplification as a method for the detection of copy number abnormalities in B-cell precursor acute lymphoblastic leukemia","volume":"49","author":"Schwab","year":"2010","journal-title":"Geneschromosomes Cancer"},{"key":"ref_31","first-page":"1","article-title":"El problema de la reca\u00edda en la leucemia linfobl\u00e1stica aguda de la infancia","volume":"18","year":"2017","journal-title":"Rev. De Hematol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1158\/1078-0432.CCR-10-1203","article-title":"New strategies in acute lymphoblastic leukemia: Translating advances in genomics into clinical practice","volume":"17","author":"Mullighan","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1056\/NEJMra052603","article-title":"Treatment of acute lymphoblastic leukemia","volume":"354","author":"Pui","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1016\/S0140-6736(12)62187-4","article-title":"Acute lymphoblastic leukaemia","volume":"381","author":"Inaba","year":"2013","journal-title":"Lancet"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1182\/bloodadvances.2019001008","article-title":"The application of RNA sequencing for the diagnosis and genomic classification of pediatric acute lymphoblastic leukemia","volume":"4","author":"Brown","year":"2020","journal-title":"Blood Adv."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e583","DOI":"10.1038\/bcj.2017.62","article-title":"Clinical and prognostic significance of e1a2 BCR-ABL1 transcript subtype in chronic myeloid leukemia","volume":"7","author":"Gong","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1111\/bjh.12250","article-title":"The distribution of MLL breakpoints correlates with outcome in infant acute leukaemia","volume":"161","author":"Emerenciano","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/leu.2017.213","article-title":"The MLL recombinome of acute leukemias in 2017","volume":"32","author":"Meyer","year":"2018","journal-title":"Leukemia"},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/ng.3230","article-title":"The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias","volume":"47","author":"Andersson","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"13886","DOI":"10.18632\/oncotarget.7356","article-title":"Prognostic and therapeutic role of targetable lesions in B-lineage acute lymphoblastic leukemia without recurrent fusion genes","volume":"7","author":"Messina","year":"2016","journal-title":"Oncotarget"},{"key":"ref_42","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_43","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1200\/JCO.2017.74.3617","article-title":"IKZF1(plus) 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_44","doi-asserted-by":"crossref","first-page":"565","DOI":"10.3324\/haematol.2017.185603","article-title":"The many faces of IKZF1 in B-cell precursor acute lymphoblastic leukemia","volume":"103","author":"Marke","year":"2018","journal-title":"Haematologica"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5312","DOI":"10.1182\/blood-2009-09-245944","article-title":"Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic\/Latino ethnicity, and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia","volume":"115","author":"Harvey","year":"2010","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5393","DOI":"10.1182\/blood-2009-11-256131","article-title":"Presence of the P2RY8-CRLF2 rearrangement is associated with a poor prognosis in non-high-risk precursor B-cell acute lymphoblastic leukemia in children treated according to the ALL-BFM 2000 protocol","volume":"115","author":"Cario","year":"2010","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Meyer, L.K., Delgado-Martin, C., Maude, S.L., Shannon, K.M., Teachey, D.T., and Hermiston, M.L. (2019). CRLF2 rearrangement in Ph-like acute lymphoblastic leukemia predicts relative glucocorticoid resistance that is overcome with MEK or Akt inhibition. 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