{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:39:03Z","timestamp":1789015143244,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Adult T\u2010cell leukemia\/lymphoma (ATL) is an intractable T\u2010cell malignancy caused by long\u2010term infection with human T\u2010cell leukemia virus type\u20101 (HTLV\u20101). While ATL pathogenesis has been associated with HTLV\u20101\u2010derived oncogenic proteins, including Tax and HBZ, the contribution of genomic aberrations remains poorly defined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To elucidate the genomic basis of ATL, whole exome sequencing was performed on cells from 47 patients with aggressive ATL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We discovered the novel mutation <jats:italic>RLTPR<\/jats:italic> Q575E in four patients (8.5%) with a median variant allele frequency of 0.52 (range 0.11\u20100.68). Despite being reported in cutaneous T\u2010cell lymphoma, three ATL patients carrying <jats:italic>RLTPR<\/jats:italic> Q575E lacked skin involvement. Patients carrying <jats:italic>RLTPR<\/jats:italic> Q575E also harbored <jats:italic>CARD11<\/jats:italic> (75%), <jats:italic>PLCG1<\/jats:italic> (25%), <jats:italic>PRKCB<\/jats:italic> (25%), or <jats:italic>IKBKB<\/jats:italic> (25%) mutations related to TCR\/NF\u2010\u03baB signaling. Jurkat cells transfected with <jats:italic>RLTPR<\/jats:italic> Q575E cDNA displayed increased NF\u2010\u03baB activity and significantly increased IL\u20102 mRNA levels under stimulation. RLTPR Q575E increased the interaction between RLTPR and CARD11, while RLTPR directly interacted with Tax.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified, and functionally validated, a novel gain\u2010of\u2010function mutation in patients with aggressive ATL. During TCR activation by Tax or gain\u2010of\u2010function mutations, <jats:italic>RLTPR<\/jats:italic> Q575E selectively upregulates NF\u2010\u03baB signaling and may exert oncogenic effects on ATL pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.13540","type":"journal-article","created":{"date-parts":[[2020,10,24]],"date-time":"2020-10-24T18:55:41Z","timestamp":1603565741000},"page":"221-229","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<i>RLTPR<\/i> Q575E: A novel recurrent gain\u2010of\u2010function mutation in patients with adult T\u2010cell leukemia\/lymphoma"],"prefix":"10.1111","volume":"106","author":[{"given":"Yuichiro","family":"Uchida","sequence":"first","affiliation":[{"name":"Department of Hematology and Rheumatology Graduate School of Medical and Dental Sciences Kagoshima University Kagoshima 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