{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T11:49:11Z","timestamp":1784029751857,"version":"3.55.0"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["NCN 2018\/29\/B\/NZ5\/02706"],"award-info":[{"award-number":["NCN 2018\/29\/B\/NZ5\/02706"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010621","name":"Uniwersytet Medyczny w Lublinie","doi-asserted-by":"publisher","award":["PBsd250"],"award-info":[{"award-number":["PBsd250"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010621","name":"Uniwersytet Medyczny w Lublinie","doi-asserted-by":"publisher","award":["DS462"],"award-info":[{"award-number":["DS462"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objectives<\/jats:title>\n<jats:p>Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease with heterogeneous clinical course. Recent studies revealed a link between <jats:italic>NOTCH1<\/jats:italic> mutation and the overexpression of <jats:italic>MYC<\/jats:italic> and <jats:italic>MYC<\/jats:italic>-related genes involved in ribosome biogenesis and protein biosynthesis, such as nucleophosmin-1 (<jats:italic>NPM1)<\/jats:italic>, in CLL cells. In the present study, we aim to evaluate the impact of the <jats:italic>NOTCH1<\/jats:italic> mutation on the <jats:italic>MYC<\/jats:italic> and <jats:italic>MYC<\/jats:italic> induced <jats:italic>NPM1<\/jats:italic> expression in CLL cells via quantification of their transcripts.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Using qRT-PCR, we analyzed the levels of <jats:italic>MYC<\/jats:italic> and three main <jats:italic>NPM1<\/jats:italic> splice variants in 214 samples collected from CLL patients. We assessed the impact of each splice variant on CLL prognostic markers, including the <jats:italic>IGHV<\/jats:italic>, <jats:italic>TP53<\/jats:italic>, <jats:italic>NOTCH1<\/jats:italic>, <jats:italic>SF3B1<\/jats:italic>, and <jats:italic>MYD88<\/jats:italic> mutational status, cytogenetic aberrations, and laboratory features.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Significantly higher levels of <jats:italic>NPM1<\/jats:italic>.<jats:italic>R1<\/jats:italic> transcripts in patients with unmutated compared to mutated <jats:italic>IGHV<\/jats:italic> status were found. The median time to first treatment (TTFT) in patients with a high level of <jats:italic>NPM1<\/jats:italic>.<jats:italic>R1<\/jats:italic> was significantly shorter compared to the group with low <jats:italic>NPM1<\/jats:italic>.<jats:italic>R1<\/jats:italic> levels (1.5 vs 33 months, p = 0.0002). Moreover, in Multivariate Cox Proportional Hazard Regression Model <jats:italic>NPM1<\/jats:italic>.<jats:italic>R1<\/jats:italic> splice variant provided an independent prognostic value for TTFT.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>In conclusion, our study indicates the prognostic significance of the level of <jats:italic>NPM1<\/jats:italic>.<jats:italic>R1<\/jats:italic> expression and suggests the importance of splicing alterations in the pathogenesis of CLL.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0276674","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T17:25:11Z","timestamp":1666718711000},"page":"e0276674","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["The role of NPM1 alternative splicing in patients with chronic lymphocytic leukemia"],"prefix":"10.1371","volume":"17","author":[{"given":"Monika","family":"Szelest","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Masternak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Zaj\u0105c","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Chojnacki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Sk\u00f3rka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Zaleska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Karczmarczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gra\u017cyna","family":"Stasiak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Wawrzyniak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Kotkowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Siemieniuk-Ry\u015b","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Purkot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5225-3921","authenticated-orcid":true,"given":"Edyta","family":"Subocz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edyta","family":"Cichocka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waldemar","family":"Tomczak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Zawirska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8758-6539","authenticated-orcid":true,"given":"Krzysztof","family":"Giannopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,10,25]]},"reference":[{"issue":"11","key":"pone.0276674.ref001","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1002\/ajh.25595","article-title":"Chronic lymphocytic leukemia: 2020 update on diagnosis, risk stratification, and treatment","volume":"94","author":"M. 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