{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:35:45Z","timestamp":1790516145773,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,5,7]],"date-time":"2015-05-07T00:00:00Z","timestamp":1430956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:p>Hairy cell leukemia (HCL) is a rare chronic B\u2010cell lymphoproliferative disorder of unclear pathogenesis. Recent studies have identified BRAF(V600E) mutations in most HCL patients, highlighting this abnormality as a molecular hallmark for this disease. Cell lines originating from HCL patients lack BRAF mutations but retain the typical piliferous morphology and the distinctive HCL immunophenotype, thus, constituting suitable tools for identifying alternative tumor genes and leukemic mechanisms in this malignancy. To this end, we integrated genomic and transcriptional profiling of the HCL cell line MLMA. The expression levels of genomically targeted genes were compared to four HCL control cell lines, thus, identifying 91 chromosomally deregulated genes. Gene set enrichment analysis of these indicted apoptosis, proliferation, and DNA damage response as altered processes. Accordingly, prominent target genes overexpressed in this cell line include <jats:italic>ATM, BRAF, CDK6, CUTL1\/CUX1, H2AFX<\/jats:italic>, and <jats:italic>REL<\/jats:italic>. Treatment of MLMA with selective pharmacological inhibitors and specific siRNA\u2010mediated gene knockdowns highlighted a central role for NFkB in their deregulation in HCL. Moreover, relevant expression profiling data from HCL and ABC\u2010DLBCL cell lines display elevated NFkB\u2010pathway activity when compared to GC\u2010DLBCL equivalents. Finally, analysis of HCL patient samples in silico collectively supported the clinical significance of NFkB activation in this disease. In conclusion, we identified deregulated genes and multiple mechanisms underlying aberrantly activated NFkB\u2010pathway in HCL. Therefore, NFkB may represent a B\u2010cell specific hallmark of HCL and a promising novel therapeutic target, most notably in patients lacking BRAF mutations in this entity including variant HCL. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/gcc.22253","type":"journal-article","created":{"date-parts":[[2015,5,8]],"date-time":"2015-05-08T05:02:42Z","timestamp":1431061362000},"page":"418-432","source":"Crossref","is-referenced-by-count":15,"title":["NFkB is activated by multiple mechanisms in hairy cell leukemia"],"prefix":"10.1002","volume":"54","author":[{"given":"Stefan","family":"Nagel","sequence":"first","affiliation":[{"name":"Department of Human and Animal Cell Lines Leibniz\u2010Institute DSMZ \u2013 German Collection of Microorganisms and Cell Cultures Braunschweig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Ehrentraut","sequence":"additional","affiliation":[{"name":"Department of Human and Animal Cell Lines 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