{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T01:48:08Z","timestamp":1768700888340,"version":"3.49.0"},"reference-count":33,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,2,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia\/lymphoma (ATL). The HTLV-1 viral trans-activator\/oncoprotein Tax is a major driver of ATL, yet it induces rapid p21Cip1\/Waf1 (p21)- and p27Kip1-mediated cellular senescence through constitutive activation (hyperactivation) of NF-\u03baB. Although constitutive NF-\u03baB activation is a common feature of T\/B-cell leukemia\/lymphoma, including ATL, it is not known how ATL cells maintain chronic NF-\u03baB activation without undergoing senescence. Here, we demonstrate that, in contrast to HTLV-1\u2212 T-cell lines, ATL cell lines no longer undergo Tax-induced senescence. Although Tax+ and Tax\u2212 ATL cell lines showed signatures of constitutive NF-\u03baB activation, their ability to progress through the cell cycle was unaffected. In some cases, ATL cell lines continued to proliferate despite significant upregulation of p21; additionally, many cell lines displayed altered expression of G1 and G1\/S cyclins, particularly overexpression of cyclin D2. We propose that, during the course of ATL development, leukemia cells acquire genetic\/epigenetic changes that can mitigate the senescence response triggered by NF-\u03baB hyperactivation. Restoring the NF-\u03baB\u2013induced senescence response would likely help to control the development and progression of ATL and similar lymphoid malignancies.<\/jats:p>","DOI":"10.1182\/bloodadvances.2018029322","type":"journal-article","created":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T16:45:26Z","timestamp":1550681126000},"page":"564-569","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":16,"title":["Cells of adult T-cell leukemia evade HTLV-1 Tax\/NF-\u03baB hyperactivation\u2013induced senescence"],"prefix":"10.1182","volume":"3","author":[{"given":"Abigail M. Druck","family":"Shudofsky","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9656-5097","authenticated-orcid":false,"given":"Chou-Zen","family":"Giam","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","published-online":{"date-parts":[[2019,2,20]]},"reference":[{"issue":"18","key":"2020021108341548700_B1","doi-asserted-by":"crossref","first-page":"3324","DOI":"10.1111\/febs.14492","article-title":"NF-\u03baB signaling mechanisms in HTLV-1-induced adult T-cell leukemia\/lymphoma","volume":"285","author":"Harhaj","year":"2018","journal-title":"FEBS 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