{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:39:38Z","timestamp":1792787978030,"version":"4.5.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009553","name":"Czech Health Research Council","doi-asserted-by":"crossref","award":["NU21-03-00128"],"award-info":[{"award-number":["NU21-03-00128"]}],"id":[{"id":"10.13039\/501100009553","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007397","name":"Charles University","doi-asserted-by":"crossref","award":["GAUK 327322"],"award-info":[{"award-number":["GAUK 327322"]}],"id":[{"id":"10.13039\/100007397","id-type":"DOI","asserted-by":"crossref"}]},{"name":"MH CZ \u2013 DRO","award":["IHBT, 00023736"],"award-info":[{"award-number":["IHBT, 00023736"]}]},{"name":"Ministry of Health, Czech Republic","award":["00064203"],"award-info":[{"award-number":["00064203"]}]},{"name":"National Institute for Cancer Research","award":["Program EXCELES, ID Project No. LX22NPO5102"],"award-info":[{"award-number":["Program EXCELES, ID Project No. LX22NPO5102"]}]},{"DOI":"10.13039\/501100001111","name":"Cancer Australia","doi-asserted-by":"publisher","award":["PdCCRS1128727"],"award-info":[{"award-number":["PdCCRS1128727"]}],"id":[{"id":"10.13039\/501100001111","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Cancer"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>BCR::ABL1<\/jats:italic>\n                      is a hallmark of chronic myeloid leukemia (CML) and is also found in acute lymphoblastic leukemia (ALL). Most genomic breaks on the\n                      <jats:italic>BCR<\/jats:italic>\n                      side occur in two regions - Major and minor - leading to p210 and p190 fusion proteins, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      By multiplex long-distance PCR or next-generation sequencing technology we characterized the\n                      <jats:italic>BCR::ABL1<\/jats:italic>\n                      genomic fusion in 971 patients (adults and children, with CML and ALL: pediatric ALL:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009353; pediatric CML:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009197; adult ALL:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009166; adult CML:\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009255 patients) and designed \u201cBreak-App\u201d web tool to allow visualization and various analyses of the breakpoints. Pearson\u2019s Chi-Squared test, Kolmogorov-Smirnov test and logistic regression were used for statistical analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Detailed analysis showed a non-random distribution of breaks in both\n                      <jats:italic>BCR<\/jats:italic>\n                      regions, whereas\n                      <jats:italic>ABL1<\/jats:italic>\n                      breaks were distributed more evenly. However, we found a significant difference in the distribution of breaks between CML and ALL. We found no association of breakpoints with any type of interspersed repeats or DNA motifs. With a few exceptions, the primary structure of the fusions suggests non-homologous end joining being responsible for the\n                      <jats:italic>BCR<\/jats:italic>\n                      and\n                      <jats:italic>ABL1<\/jats:italic>\n                      gene fusions. Analysis of reciprocal\n                      <jats:italic>ABL1::BCR<\/jats:italic>\n                      fusions in 453 patients showed mostly balanced translocations without major deletions or duplications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Taken together, our data suggest that physical colocalization and chromatin accessibility, which change with the developmental stage of the cell (hence the difference between ALL and CML), are more critical factors influencing breakpoint localization than presence of specific DNA motifs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12943-024-02053-4","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T03:01:49Z","timestamp":1720148509000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Distinct pattern of genomic breakpoints in CML and BCR::ABL1-positive ALL: analysis of 971 patients"],"prefix":"10.1186","volume":"23","author":[{"given":"Lenka","family":"Hovorkova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Winkowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justina","family":"Skorepova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Krumbholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adela","family":"Benesova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaclava","family":"Polivkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Alten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Bardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rathana","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toby N.","family":"Trahair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Clappier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Chiaretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Henderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Sutton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Sramkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Stary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina Machova","family":"Polakova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Marschalek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Metzler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Cazzaniga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Cario","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Trka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marketa","family":"Zaliova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Zuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"issue":"11","key":"2053_CR1","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1016\/j.dnarep.2011.08.010","volume":"10","author":"T Burmeister","year":"2011","unstructured":"Burmeister T, Groger D, Kuhn A, Hoelzer D, Thiel E, Reinhardt R. Fine structure of translocation breakpoints within the major breakpoint region in BCR-ABL1-positive leukemias. DNA Repair (Amst). 2011;10(11):1131\u20137.","journal-title":"DNA Repair (Amst)"},{"issue":"10","key":"2053_CR2","doi-asserted-by":"publisher","first-page":"1742","DOI":"10.1038\/leu.2010.174","volume":"24","author":"J Score","year":"2010","unstructured":"Score J, Calasanz MJ, Ottman O, Pane F, Yeh RF, Sobrinho-Simoes MA, et al. Analysis of genomic breakpoints in p190 and p210 BCR-ABL indicate distinct mechanisms of formation. Leukemia. 2010;24(10):1742\u201350.","journal-title":"Leukemia"},{"issue":"10","key":"2053_CR3","first-page":"14321","volume":"14","author":"M Krumbholz","year":"2019","unstructured":"Krumbholz M, Goerlitz K, Albert C, Lawlor J, Suttorp M, Metzler M. Large amplicon droplet digital PCR for DNA-based monitoring of pediatric chronic myeloid leukaemia. 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Informed consent was obtained following the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"138"}}