{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T02:46:20Z","timestamp":1774579580106,"version":"3.50.1"},"reference-count":72,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2015\/19\/N\/NZ5\/03495"],"award-info":[{"award-number":["2015\/19\/N\/NZ5\/03495"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Adult acute lymphoblastic leukemia (ALL) is associated with poor outcomes. ALL is initiated by primary aberrations, but secondary genetic lesions are necessary for overt ALL. In this study, we reassessed the value of primary and secondary aberrations in intensively treated ALL patients in relation to mutator enzyme expression. RT-PCR, genomic PCR, and sequencing were applied to evaluate primary aberrations, while qPCR was used to measure the expression of RAG and AID mutator enzymes in 166 adult ALL patients. Secondary copy number alterations (CNA) were studied in 94 cases by MLPA assay. Primary aberrations alone stratified 30% of the patients (27% high-risk, 3% low-risk cases). The remaining 70% intermediate-risk patients included BCR::ABL1pos subgroup and ALL lacking identified genetic markers (NEG ALL). We identified three CNA profiles: high-risk bad-CNA (CNAhigh\/IKZF1pos), low-risk good-CNA (all other CNAs), and intermediate-risk CNAneg. Furthermore, based on RAG\/AID expression, we report possible mechanisms underlying the CNA profiles associated with poor outcome: AID stratified outcome in CNAneg, which accompanied most likely a particular profile of single nucleotide variations, while RAG in CNApos increased the odds for CNAhigh\/IKZF1pos development. Finally, we integrated primary genetic aberrations with CNA to propose a revised risk stratification code, which allowed us to stratify 75% of BCR::ABL1pos and NEG patients.<\/jats:p>","DOI":"10.3390\/cancers15225431","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T10:57:46Z","timestamp":1700045866000},"page":"5431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Prognostic Impact of Copy Number Alterations\u2019 Profile and AID\/RAG Signatures in Acute Lymphoblastic Leukemia (ALL) with BCR::ABL and without Recurrent Genetic Aberrations (NEG ALL) Treated with Intensive Chemotherapy"],"prefix":"10.3390","volume":"15","author":[{"given":"Marta","family":"Libura","sequence":"first","affiliation":[{"name":"Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolina","family":"Karabin","sequence":"additional","affiliation":[{"name":"Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2341-6976","authenticated-orcid":false,"given":"Pawe\u0142","family":"Tyrna","sequence":"additional","affiliation":[{"name":"Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6641-0182","authenticated-orcid":false,"given":"Anna","family":"Czy\u017c","sequence":"additional","affiliation":[{"name":"Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Medical University of Wroc\u0142aw, 50-137 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"Makuch-\u0141asica","sequence":"additional","affiliation":[{"name":"Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo\u017cena","family":"Ja\u017awiec","sequence":"additional","affiliation":[{"name":"Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Medical University of Wroc\u0142aw, 50-137 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Paluszewska","sequence":"additional","affiliation":[{"name":"Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beata","family":"Pi\u0105tkowska-Jakubas","sequence":"additional","affiliation":[{"name":"Department of Hematology, Jagiellonian University Medical College, 31-008 Cracow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9105-1767","authenticated-orcid":false,"given":"Magdalena","family":"Zawada","sequence":"additional","affiliation":[{"name":"Department of Hematology, Jagiellonian University Medical College, 31-008 Cracow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micha\u0142","family":"Gniot","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, Pozna\u0144 University of Medical Sciences, 61-701 Pozna\u0144, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9848-3674","authenticated-orcid":false,"given":"Joanna","family":"Trubicka","sequence":"additional","affiliation":[{"name":"Children\u2019s Memorial Health Institute, 04-736 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3646-4902","authenticated-orcid":false,"given":"Magdalena","family":"Szyma\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Borg","sequence":"additional","affiliation":[{"name":"Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Wi\u0119sik","sequence":"additional","affiliation":[{"name":"Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylwia","family":"Czekalska","sequence":"additional","affiliation":[{"name":"Department of Hematology, Jagiellonian University Medical College, 31-008 Cracow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izabela","family":"Florek","sequence":"additional","affiliation":[{"name":"Department of Hematology, Jagiellonian University Medical College, 31-008 Cracow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Kr\u00f3l","sequence":"additional","affiliation":[{"name":"Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u0142gorzata","family":"Paszkowska-Kowalewska","sequence":"additional","affiliation":[{"name":"Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidia","family":"Gil","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, Pozna\u0144 University of Medical Sciences, 61-701 Pozna\u0144, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Kapelko-S\u0142owik","sequence":"additional","affiliation":[{"name":"Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Medical University of Wroc\u0142aw, 50-137 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8691-4310","authenticated-orcid":false,"given":"El\u017cbieta","family":"Patkowska","sequence":"additional","affiliation":[{"name":"Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Tomaszewska","sequence":"additional","affiliation":[{"name":"Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krzysztof","family":"M\u0105dry","sequence":"additional","affiliation":[{"name":"Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafa\u0142","family":"Machowicz","sequence":"additional","affiliation":[{"name":"Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3108-4035","authenticated-orcid":false,"given":"Tomasz","family":"Czerw","sequence":"additional","affiliation":[{"name":"Maria Sk\u0142odowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1593-8005","authenticated-orcid":false,"given":"Agnieszka","family":"Piekarska","sequence":"additional","affiliation":[{"name":"Department of Hematology and Transplantology, Medical University of Gda\u0144sk, 80-214 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8112-3974","authenticated-orcid":false,"given":"Magdalena","family":"Dutka","sequence":"additional","affiliation":[{"name":"Department of Hematology and Transplantology, Medical University of Gda\u0144sk, 80-214 Gda\u0144sk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Kopi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, 40-032 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grzegorz","family":"Helbig","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, 40-032 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Gromek","sequence":"additional","affiliation":[{"name":"Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, 20-081 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0992-2020","authenticated-orcid":false,"given":"Krzysztof","family":"Lewandowski","sequence":"additional","affiliation":[{"name":"Department of Hematology and Bone Marrow Transplantation, Pozna\u0144 University of Medical Sciences, 61-701 Pozna\u0144, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Zacharczuk","sequence":"additional","affiliation":[{"name":"Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Medical University of Wroc\u0142aw, 50-137 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0519-1104","authenticated-orcid":false,"given":"Anna","family":"Pastwi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology and Genetics, Medical University of Warsaw, 02-106 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Wr\u00f3bel","sequence":"additional","affiliation":[{"name":"Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Medical University of Wroc\u0142aw, 50-137 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Haus","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 87-100 Toru\u0144, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3858-8180","authenticated-orcid":false,"given":"Grzegorz","family":"Basak","sequence":"additional","affiliation":[{"name":"Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerzy","family":"Ho\u0142owiecki","sequence":"additional","affiliation":[{"name":"Maria Sk\u0142odowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7215-0444","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"Juszczy\u0144ski","sequence":"additional","affiliation":[{"name":"Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Lech-Mara\u0144da","sequence":"additional","affiliation":[{"name":"Institute of Hematology and Transfusion Medicine, 02-776 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Giebel","sequence":"additional","affiliation":[{"name":"Maria Sk\u0142odowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-102 Gliwice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wies\u0142aw Wiktor","family":"J\u0119drzejczak","sequence":"additional","affiliation":[{"name":"Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/nrclinonc.2015.38","article-title":"Genomics in Acute Lymphoblastic Leukaemia: Insights and Treatment Implications","volume":"12","author":"Roberts","year":"2015","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s41375-021-01448-2","article-title":"Prognostic Impact of Chromosomal Abnormalities and Copy Number Alterations in Adult B-Cell Precursor Acute Lymphoblastic Leukaemia: A UKALL14 Study","volume":"36","author":"Moorman","year":"2022","journal-title":"Leukemia"},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"3739","DOI":"10.1182\/blood-2014-01-547695","article-title":"Oncogenetics and Minimal Residual Disease Are Independent Outcome Predictors in Adult Patients with Acute Lymphoblastic Leukemia","volume":"123","author":"Beldjord","year":"2014","journal-title":"Blood"},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1200\/JCO.2016.70.7836","article-title":"Genetic Basis of Acute Lymphoblastic Leukemia","volume":"35","author":"Iacobucci","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.3324\/haematol.2021.279177","article-title":"Genetic and Genomic Analysis of Acute Lymphoblastic Leukemia in Older Adults Reveals a Distinct Profile of Abnormalities: Analysis of 210 Patients from the UKALL14 and UKALL60+ Clinical Trials","volume":"107","author":"Creasey","year":"2022","journal-title":"Haematologica"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.4065\/80.11.1517","article-title":"Adult Acute Lymphoblastic Leukemia","volume":"Volume 80","author":"Jabbour","year":"2005","journal-title":"Mayo Clinic Proceedings"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1097\/MOH.0b013e3283034697","article-title":"Progress in the Treatment of Adults with Acute Lymphoblastic Leukemia","volume":"15","author":"Larson","year":"2008","journal-title":"Curr. Opin. Hematol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1182\/asheducation-2018.1.137","article-title":"Genetics and Prognosis of ALL in Children vs. Adults","volume":"201","author":"Roberts","year":"2018","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13045-023-01409-5","article-title":"The Evolution of Acute Lymphoblastic Leukemia Research and Therapy at MD Anderson over Four Decades","volume":"16","author":"Jabbour","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"35445","DOI":"10.18632\/oncotarget.16367","article-title":"Pathogenesis of ETV6\/RUNX1-Positive Childhood Acute Lymphoblastic Leukemia and Mechanisms Underlying Its Relapse","volume":"8","author":"Sun","year":"2017","journal-title":"Oncotarget"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/ni.3160","article-title":"Mechanisms of Clonal Evolution in Childhood Acute Lymphoblastic Leukemia","volume":"16","author":"Swaminathan","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/nature09733","article-title":"Evolution of Human BCR-ABL1 Lymphoblastic Leukaemia-Initiating Cells","volume":"469","author":"Notta","year":"2011","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"407","DOI":"10.3324\/haematol.2015.141101","article-title":"New and Emerging Prognostic and Predictive Genetic Biomarkers in B-Cell Precursor Acute Lymphoblastic Leukemia","volume":"101","author":"Moorman","year":"2016","journal-title":"Haematologica"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/nature05690","article-title":"Genome-Wide Analysis of Genetic Alterations in Acute Lymphoblastic Leukaemia","volume":"446","author":"Mullighan","year":"2007","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1182\/blood-2008-08-173963","article-title":"Identification and Molecular Characterization of Recurrent Genomic Deletions on 7p12 in the IKZF1 Gene in a Large Cohort of BCR-ABL1-Positive Acute Lymphoblastic Leukemia Patients: On Behalf of Gruppo Italiano Malattie Ematologiche Dell\u2019Adulto Acute Leukemia Working Party (GIMEMA AL WP)","volume":"114","author":"Iacobucci","year":"2009","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/nature09650","article-title":"Genetic Variegation of Clonal Architecture and Propagating Cells in Leukaemia","volume":"469","author":"Anderson","year":"2011","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.leukres.2017.01.034","article-title":"Genomic Analysis of Adult B-ALL Identifies Potential Markers of Shorter Survival","volume":"56","author":"Patel","year":"2017","journal-title":"Leuk. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"874771","DOI":"10.3389\/fped.2022.874771","article-title":"Immunoglobulin Heavy Chain High-Throughput Sequencing in Pediatric B-Precursor Acute Lymphoblastic Leukemia: Is the Clonality of the Disease at Diagnosis Related to Its Prognosis?","volume":"10","author":"Levy","year":"2022","journal-title":"Front. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4178","DOI":"10.1182\/blood-2008-06-165027","article-title":"Genome-Wide Copy Number Profiling Reveals Molecular Evolution from Diagnosis to Relapse in Childhood Acute Lymphoblastic Leukemia","volume":"112","author":"Yang","year":"2008","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/ng.2874","article-title":"RAG-Mediated Recombination Is the Predominant Driver of Oncogenic Rearrangement in ETV6-RUNX1 Acute Lymphoblastic Leukemia","volume":"46","author":"Papaemmanuil","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"18470","DOI":"10.1074\/jbc.274.26.18470","article-title":"Specific Expression of Activation-Induced Cytidine Deaminase (AID), a Novel Member of the RNA-Editing Deaminase Family in Germinal Center B Cells","volume":"274","author":"Muramatsu","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0065-2776(10)05006-6","article-title":"AID and Somatic Hypermutation","volume":"105","author":"Maul","year":"2010","journal-title":"Adv. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7411","DOI":"10.1158\/0008-5472.CAN-10-1438","article-title":"Activation-Induced Cytidine Deaminase Accelerates Clonal Evolution in BCR-ABL1-Driven B-Cell Lineage Acute Lymphoblastic Leukemia","volume":"70","author":"Gruber","year":"2010","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1016\/j.cell.2008.10.035","article-title":"Human Chromosomal Translocations at CpG Sites and a Theoretical Basis for Their Lineage and Stage Specificity","volume":"135","author":"Tsai","year":"2008","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4060","DOI":"10.1182\/bloodadvances.2021005017","article-title":"Inflammation Accelerates BCR-ABL11 B-ALL Development through Upregulation of AID","volume":"6","author":"Zhang","year":"2022","journal-title":"Blood Adv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/cei.12812","article-title":"Illegitimate RAG-Mediated Recombination Events Are Involved in IKZF1 Delta 3\u20136 Deletion in BCR-ABL1 Lymphoblastic Leukaemia","volume":"185","author":"Dong","year":"2016","journal-title":"Clin. Exp. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/nature06866","article-title":"BCR-ABL1 Lymphoblastic Leukaemia Is Characterized by the Deletion of Ikaros","volume":"453","author":"Mullighan","year":"2008","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4067","DOI":"10.1182\/blood.V128.22.4067.4067","article-title":"Extensive RAG-Mediated Rearrangements and Mutations in BCR-ABL1 and BCR-ABL1-like Adult Acute Lymphoblastic Leukemia","volume":"128","author":"Sanders","year":"2016","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1038\/s41588-023-01429-4","article-title":"Transcriptomic Classes of BCR-ABL1 Lymphoblastic Leukemia","volume":"55","author":"Kim","year":"2023","journal-title":"Nat. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1056\/NEJMoa0808253","article-title":"Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia","volume":"360","author":"Mullighan","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3809","DOI":"10.1002\/cncr.29579","article-title":"Prognostic Significance of Copy Number Alterations in Adolescent and Adult Patients with Precursor B Acute Lymphoblastic Leukemia Enrolled in PETHEMA Protocols","volume":"121","author":"Ribera","year":"2015","journal-title":"Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1038\/s41409-020-01139-z","article-title":"Allogeneic HCT for Adults with B-Cell Precursor Acute Lymphoblastic Leukemia Harboring IKZF1 Gene Mutations. A Study by the Acute Leukemia Working Party of the EBMT","volume":"56","author":"Giebel","year":"2021","journal-title":"Bone Marrow Transpl."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1182\/blood.2020010144","article-title":"Molecular Classification Improves Risk Assessment in Adult BCR-ABL1\u2013 Negative B-ALL","volume":"138","author":"Paietta","year":"2021","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/bjh.14721","article-title":"Clinical Significance of Recurrent Copy Number Aberrations in B-Lineage Acute Lymphoblastic Leukaemia without Recurrent Fusion Genes across Age Cohorts","volume":"178","author":"Messina","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_37","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_38","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_39","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_40","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_41","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1038\/sj.leu.2401592","article-title":"Standardized RT-PCR Analysis of Fusion Gene Transcripts from Chromosome Aberrations in Acute Leukemia for Detection of Minimal Residual Disease Report of the BIOMED-1 Concerted Action: Investigation of Minimal Residual Disease in Acute Leukemia","volume":"13","author":"Macintyre","year":"1999","journal-title":"Leukemia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s00277-008-0540-6","article-title":"The Application of Conventional Cytogenetics, FISH, and RT-PCR to Detect Genetic Changes in 70 Children with ALL","volume":"87","author":"Soszynska","year":"2008","journal-title":"Ann. Hematol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1126\/science.2360047","article-title":"RAG-1 and RAG-2, Adjacent Genes That Synergistically Activate V(D)J Recombination","volume":"248","author":"Oettinger","year":"1990","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3847","DOI":"10.1182\/blood-2007-09-112631","article-title":"Expression of Spliced Oncogenic Ikaros Isoforms in Philadelphia-Positive Acute Lymphoblastic Leukemia Patients Treated with Tyrosine Kinase Inhibitors: Implications for a New Mechanism of Resistance","volume":"112","author":"Iacobucci","year":"2008","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1200\/JCO.2017.76.8192","article-title":"Intensified Therapy of Acute Lymphoblastic Leukemia in Adults: Report of the Randomized GRAALL-2005 Clinical Trial","volume":"36","author":"Huguet","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3324\/haematol.2014.117424","article-title":"Expression Profiling of Adult Acute Lymphoblastic Leukemia Identifies a BCR-ABL1-like Subgroup Characterized by High Non-Response and Relapse Rates","volume":"100","author":"Boer","year":"2015","journal-title":"Haematologica"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1182\/blood-2017-07-796862","article-title":"Genomic CDKN2A\/2B Deletions in Adult Ph1 All Are Adverse despite Allogeneic Stem Cell Transplantation","volume":"131","author":"Pfeifer","year":"2018","journal-title":"Blood"},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/S2352-3026(18)30176-5","article-title":"Combination of Hyper-CVAD with Ponatinib as First-Line Therapy for Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukaemia: Long-Term Follow-up of a Single-Centre, Phase 2 Study","volume":"5","author":"Jabbour","year":"2018","journal-title":"Lancet Haematol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4158","DOI":"10.1002\/cncr.29646","article-title":"Long-Term Follow-up of a Phase 2 Study of Chemotherapy plus Dasatinib for the Initial Treatment of Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia","volume":"121","author":"Ravandi","year":"2015","journal-title":"Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3644","DOI":"10.1200\/JCO.2010.28.1287","article-title":"Chemotherapy-Phased Imatinib Pulses Improve Long-Term Outcome of Adult Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Northern Italy Leukemia Group Protocol 09\/00","volume":"28","author":"Bassan","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"653","DOI":"10.3324\/haematol.2014.118588","article-title":"Final Report of a Phase II Study of Imatinib Mesylate with Hyper-CVAD for the Front-Line Treatment of Adult Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia","volume":"100","author":"Daver","year":"2015","journal-title":"Haematologica"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1182\/blood-2019-125146","article-title":"Long-Term Safety and Efficacy of Hyper-CVAD Plus Ponatinib As Frontline Therapy for Adults with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia","volume":"134","author":"Short","year":"2019","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/j.1365-2141.2008.07185.x","article-title":"Status of Minimal Residual Disease after Induction Predicts Outcome in Both Standard and High-Risk Ph-Negative Adult Acute Lymphoblastic Leukaemia. The Polish Adult Leukemia Group ALL 4-2002 MRD Study","volume":"142","author":"Holowiecki","year":"2008","journal-title":"Br. J. Haematol."},{"key":"ref_55","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_56","doi-asserted-by":"crossref","first-page":"3842","DOI":"10.7150\/jca.33989","article-title":"RAG1 High Expression Associated with IKZF1 Dysfunction in Adult B-Cell Acute Lymphoblastic Leukemia","volume":"10","author":"Han","year":"2019","journal-title":"J. Cancer"},{"key":"ref_57","first-page":"e13087","article-title":"Transcription-Coupled Genetic Instability Marks Acute Lymphoblastic Leukemia Structural Variation Hotspots","volume":"6","author":"Vuorenmaa","year":"2016","journal-title":"eLife"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41568-023-00584-4","article-title":"Gut Microbiome Immaturity and Childhood Acute Lymphoblastic Leukaemia","volume":"23","author":"Peppas","year":"2023","journal-title":"Nat. Rev. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1182\/blood.2019004381","article-title":"An Intact Gut Microbiome Protects Genetically Predisposed Mice against Leukemia","volume":"136","author":"Janssen","year":"2020","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s41568-018-0015-6","article-title":"A Causal Mechanism for Childhood Acute Lymphoblastic Leukaemia","volume":"18","author":"Greaves","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"965312","DOI":"10.3389\/fimmu.2022.965312","article-title":"Activation Induced Cytidine Deaminase: An Old Friend with New Faces","volume":"13","author":"Gunaydin","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1111\/j.1349-7006.2012.02293.x","article-title":"Inflammation-Mediated Genomic Instability: Roles of Activation-Induced Cytidine Deaminase in Carcinogenesis","volume":"103","author":"Shimizu","year":"2012","journal-title":"Cancer Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1002\/ijc.22292","article-title":"Expression of Activation-Induced Cytidine Deaminase in Human Hepatocytes during Hepatocarcinogenesis","volume":"120","author":"Kou","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"677034","DOI":"10.3389\/fonc.2021.677034","article-title":"Gene Deletions and Prognostic Values in B-Linage Acute Lymphoblastic Leukemia","volume":"11","author":"Fang","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ccell.2015.07.016","article-title":"Efficacy of Retinoids in IKZF1-Mutated BCR-ABL1 Acute Lymphoblastic Leukemia","volume":"28","author":"Churchman","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1182\/blood-2005-07-2815","article-title":"BCR\/ABL Kinase Induces Self-Mutagenesis via Reactive Oxygen Species to Encode Imatinib Resistance","volume":"108","author":"Koptyra","year":"2006","journal-title":"Blood"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1084\/jem.20110580","article-title":"Gain-of-Function Mutations in Interleukin-7 Receptor-\u03b1 (IL7R) in Childhood Acute Lymphoblastic Leukemias","volume":"208","author":"Shochat","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/ng.2532","article-title":"The Genomic Landscape of Hypodiploid Acute Lymphoblastic Leukemia","volume":"45","author":"Holmfeldt","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Iacobucci, I., Iraci, N., Messina, M., Lonetti, A., Chiaretti, S., Valli, E., Ferrari, A., Papayannidis, C., Paoloni, F., and Vitale, A. (2012). IKAROS Deletions Dictate a Unique Gene Expression Signature in Patients with Adult B-Cell Acute Lymphoblastic Leukemia. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040934"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1182\/blood-2009-08-235408","article-title":"Down Syndrome Acute Lymphoblastic Leukemia, a Highly Heterogeneous Disease in Which Aberrant Expression of CRLF2 Is Associated with Mutated JAK2: A Report from the International BFM Study Group","volume":"115","author":"Hertzberg","year":"2010","journal-title":"Blood"},{"key":"ref_71","first-page":"71","article-title":"An Improvement of the 2\u02c6(\u2212Delta Delta CT) Method for Quantitative Real-Time Polymerase Chain Reaction Data Analysis","volume":"3","author":"Rao","year":"2013","journal-title":"Biostat. Bioinform. Biomath."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/j.bbmt.2012.01.012","article-title":"Evaluation of Minimal Residual Disease by Real-Time Quantitative PCR of Wilms\u2019 Tumor 1 Expression in Patients with Acute Myelogenous Leukemia after Allogeneic Stem Cell Transplantation: Correlation with Flow Cytometry and Chimerism","volume":"18","author":"Kwon","year":"2012","journal-title":"Biol. Blood Marrow Transplant."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/22\/5431\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:23:41Z","timestamp":1760131421000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/22\/5431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,15]]},"references-count":72,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["cancers15225431"],"URL":"https:\/\/doi.org\/10.3390\/cancers15225431","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,15]]}}}