{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:04:10Z","timestamp":1770336250417,"version":"3.49.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,9,8]],"date-time":"2017-09-08T00:00:00Z","timestamp":1504828800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,9,8]],"date-time":"2017-09-08T00:00:00Z","timestamp":1504828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The genetic events that lead to aggressive transformation of cases of splenic marginal zone lymphoma (SMZL) after the chronic clinical stage have not been well understood. We aimed to find candidate genes associated with aggressive features of SMZL. We have successfully established two SMZL cell lines, designated SL-15 and SL-22, derived from the same patient\u2019s tumor clone in chronic and aggressive phases, respectively. Microarray analysis identified cell cycle-associated genes\u2014specifically <jats:italic>PLK1<\/jats:italic>\u2014as the most significantly upregulated in primary aggressive SMZL cells compared with cells from chronic phase. <jats:italic>EPHA4<\/jats:italic> and <jats:italic>MS4A1<\/jats:italic> (<jats:italic>CD20<\/jats:italic>) were found to be downregulated dramatically. These gene expression patterns were reproduced in both cell lines. Genetic knockdown of <jats:italic>PLK1<\/jats:italic> resulted in inhibition of cell proliferation and induction of apoptosis in SL-22 cells, which expressed higher levels of <jats:italic>PLK1<\/jats:italic> than SL-15 cells. SL-22 cells needed higher concentrations of chemical PLK1 inhibitors to achieve greater effects. In addition, we found homozygous deletion of the <jats:italic>MS4A1<\/jats:italic> gene as a newly identified molecular mechanism of CD20-negative conversion. Our findings are expected to stimulate further studies on whether PLK1 could be a potential therapeutic target for this tumor. Furthermore, cases with CD20-negatively converted lymphomas should be screened for the genomic loss of <jats:italic>MS4A1<\/jats:italic>.<\/jats:p>","DOI":"10.1038\/s41598-017-11389-5","type":"journal-article","created":{"date-parts":[[2017,9,4]],"date-time":"2017-09-04T14:28:12Z","timestamp":1504535292000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Differential gene expression profiling linked to tumor progression of splenic marginal zone lymphoma"],"prefix":"10.1038","volume":"7","author":[{"given":"Tomonori","family":"Higuchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumiko","family":"Hashida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayuko","family":"Taniguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikio","family":"Kamioka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Daibata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,9,8]]},"reference":[{"key":"11389_CR1","unstructured":"Isaacson, P. 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Cancer \n                           119, 629\u2013638 (2013).","journal-title":"Cancer"},{"key":"11389_CR4","doi-asserted-by":"publisher","first-page":"4643","DOI":"10.1182\/blood-2005-11-4659","volume":"107","author":"L Arcaini","year":"2006","unstructured":"Arcaini, L. et al. Splenic marginal zone lymphoma: a prognostic model for clinical use. Blood \n                           107, 4643\u20134649 (2006).","journal-title":"Blood"},{"key":"11389_CR5","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1038\/leu.2013.365","volume":"28","author":"N Mart\u00ednez","year":"2014","unstructured":"Mart\u00ednez, N. et al. Whole-exome sequencing in splenic marginal zone lymphoma reveals mutations in genes involved in marginal zone differentiation. Leukemia \n                           28, 1334\u20131340 (2014).","journal-title":"Leukemia"},{"key":"11389_CR6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0083244","volume":"8","author":"M Parry","year":"2013","unstructured":"Parry, M. et al. Whole exome sequencing identifies novel recurrently mutated genes in patients with splenic marginal zone lymphoma. PLoS One \n                           8, e83244 (2013).","journal-title":"PLoS One"},{"key":"11389_CR7","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1038\/leu.2014.330","volume":"29","author":"A Clipson","year":"2015","unstructured":"Clipson, A. et al. KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype. 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