{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T19:39:29Z","timestamp":1788205169612,"version":"build-2803163510"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["TBI-V-1-423-VBW-144"],"award-info":[{"award-number":["TBI-V-1-423-VBW-144"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Hematol Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The Philadelphia chromosome is the result of a balanced reciprocal translocation between the long arms of chromosomes 9 and 22, resulting in the fusion gene BCR-ABL1. Despite it being a hallmark of acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML) and mixed-phenotype acute leukemia, comparatively little is known about its effects, which can be directly attributed to its presence in cancer cells. To study this question, we created and characterized a Jurkat cell line carrying this alteration via a CRISPR\/Cas9-based approach. Compared with wild-type Jurkat cells, BCR-ABL1 p190-expressing cells exhibited increased proliferation and increased sensitivity to tyrosine kinase inhibitors (TKIs). By integrating gene expression, DNA methylation and protein expression data generated by next-generation sequencing (NGS) and mass spectrometry analyses, we identified a number of pathways as well as individual proteins that are altered in association with BCR-ABL1 p190. Among the deregulated proteins, we identified known cancer proteins, such as the tumor suppressors ASS1 and ABI3, which were downregulated in our model, or specifically upregulated TRBC1. Particularly noteworthy is the downregulation of CYP51A1, which is known to confer TKI resistance under normal circumstances, and therefore directly associated with increased TKI sensitivity in BCR-ABL1 p190-positive cells. Another interesting feature is SPART, whose abundance was increased despite strong promoter hypermethylation, indicating that some transcriptional changes in BCR-ABL1 p190-carrying cells occur independently of promoter methylation and reflect broader regulatory effects of the fusion.<\/jats:p>","DOI":"10.1186\/s40164-026-00758-4","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T13:02:52Z","timestamp":1771506172000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular background of Philadelphia chromosome dependent enhancement of cellular growth and tyrosine kinase inhibitor sensitivity"],"prefix":"10.1186","volume":"15","author":[{"given":"Md Faruq","family":"Hossain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Hagenau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars R.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Rhode","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Sura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela G.","family":"Salazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Tzvetkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Dunkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Simm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefine","family":"Radke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas W.","family":"Kuss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"758_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/s13039-016-0257-5","author":"X Lyu","year":"2016","unstructured":"Lyu X, et al. A novel BCR-ABL1 fusion gene identified by next-generation sequencing in chronic myeloid leukemia. Mol Cytogenet. 2016. https:\/\/doi.org\/10.1186\/s13039-016-0257-5.","journal-title":"Mol Cytogenet"},{"issue":"1","key":"758_CR2","doi-asserted-by":"publisher","first-page":"215","DOI":"10.3390\/pharmaceutics14010215","volume":"14","author":"GP Amarante-Mendes","year":"2022","unstructured":"Amarante-Mendes GP, Rana A, Datoguia TS, Hamerschlak N, Brumatti G. BCR-ABL1 tyrosine kinase complex signaling transduction: challenges to overcome resistance in chronic myeloid leukemia. Pharmaceutics. 2022;14(1):215. https:\/\/doi.org\/10.3390\/pharmaceutics14010215.","journal-title":"Pharmaceutics"},{"issue":"1","key":"758_CR3","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1182\/asheducation-2016.1.573","volume":"2016","author":"N G\u00f6kbuget","year":"2016","unstructured":"G\u00f6kbuget N. Treatment of older patients with acute lymphoblastic leukemia. Hematol Am Soc Hematol Educ Program. 2016;2016(1):573\u20139.","journal-title":"Hematol Am Soc Hematol Educ Program"},{"issue":"2","key":"758_CR4","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1182\/blood-2009-07-232124","volume":"115","author":"AV Moorman","year":"2010","unstructured":"Moorman AV, Chilton L, Wilkinson J, Ensor HM, Bown N, Proctor SJ. A population-based cytogenetic study of adults with acute lymphoblastic leukemia. Blood. 2010;115(2):206\u201314. https:\/\/doi.org\/10.1182\/blood-2009-07-232124.","journal-title":"Blood"},{"key":"758_CR5","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1186\/s12864-018-4718-6","volume":"19","author":"L Gioia","year":"2018","unstructured":"Gioia L, Siddique A, Head SR, Salomon DR, Su AI. A genome-wide survey of mutations in the Jurkat cell line. 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