{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T03:30:08Z","timestamp":1775446208141,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Adult T\u2010cell leukemia (ATL), caused by human T\u2010cell leukemia virus type 1 (HTLV\u20101), has a poorer prognosis than other peripheral T\u2010cell lymphomas. Phosphorylation of highly expressed in cancer 1 (Hec1) by NIMA\u2010related kinase 2 (Nek2) is essential for mitosis. This study evaluated the therapeutic potential of Nek2 and Hec1 inhibitors in ATL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cell proliferation, survival, cell cycle progression, apoptosis, mitochondrial membrane potential, and reactive oxygen species (ROS) were assessed. Expression of Nek2, Hec1, and related signaling proteins was also analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nek2 and Hec1 were upregulated in HTLV\u20101\u2010infected T\u2010cell lines and in normal peripheral blood mononuclear cells after infection. Knockdown of Nek2 or treatment with Nek2\/Hec1 inhibitors (INH154, T\u20101101 tosylate) or the Nek2 inhibitor MBM\u201055S reduced proliferation and survival. INH154 induced Nek2 degradation and G1\u2010phase arrest, accompanied by downregulation of CDK2\/4, cyclin D2\/E, c\u2010Myc, and phospho\u2010pRb, and upregulation of p53. It also triggered apoptosis via caspase activation, downregulation of Mcl\u20101, survivin, and c\u2010IAP2, and upregulation of Bax and Bak. Additionally, INH154 induced necroptosis, ROS accumulation, DNA damage, mitochondrial dysfunction, and suppression of \u03b2\u2010catenin and NF\u2010\u03baB\/AP\u20101 signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Aberrant expression of Nek2 and Hec1 may contribute to ATL pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ejh.70124","type":"journal-article","created":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T02:49:48Z","timestamp":1769222988000},"page":"635-645","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of Nek2 and Hec1 in\n                    <scp>HTLV<\/scp>\n                    \u20101\u2010Infected T\u2010Cell Lines"],"prefix":"10.1111","volume":"116","author":[{"given":"Chie","family":"Ishikawa","sequence":"first","affiliation":[{"name":"Department of Microbiology and Oncology, Graduate School of Medicine University of the Ryukyus  Ginowan Japan"},{"name":"Research Facility Center University of the Ryukyus  Nishihara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3998-6711","authenticated-orcid":false,"given":"Naoki","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Oncology, Graduate School of Medicine University of the Ryukyus  Ginowan Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2025.107680"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2025.107642"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2024.107635"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/v16101616"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2024.107598"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.02686"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12777"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.117287"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2024.07.013"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2022.188696"},{"key":"e_1_2_11_12_1","first-page":"17","article-title":"The NEK Family of Serine\/Threonine Kinases as a Biomarker for Cancer","volume":"23","author":"Panchal N. 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