{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:43:29Z","timestamp":1785408209137,"version":"3.56.0"},"posted":{"date-parts":[[2025,12,23]]},"group-title":"Cancer Biology","reference-count":98,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01 CA127621"],"award-info":[{"award-number":["R01 CA127621"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/00y27w112","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Species C adenoviruses infect virtually all children in the first few years of life. These viruses can establish asymptomatic persistent infections in mucosal-associated lymphocytes and can infect lymphocytes\n                  <jats:italic>in utero<\/jats:italic>\n                  . Although adenovirus is a DNA tumor virus, it has not yet been shown to initiate cancer in humans. Epidemiological studies of B cell precursor acute lymphoblastic leukemia (ALL), point towards an infectious etiology. The ETV6\/RUNX1 fusion protein results from a chromosomal translocation t(12; 21) believed to initiate ALL. This translocation can be detected\n                  <jats:italic>in utero<\/jats:italic>\n                  and has been identified in as much as 40% of clustered cases of leukemia, which are those most likely to have been initiated by an infectious agent. Infectious agents have not yet been detected in leukemic cells, causing speculation that the oncogenic agent has been lost in the transformed progeny through a \u201chit and run\u201d mechanism. In the current study, we attempt to model the \u201crun\u201d of adenovirus in B-lymphocytes by forcing expression of leukemic fusion genes to determine if they create an environment that is refractory to adenovirus persistence. Here we show that the common leukemic fusion proteins, ETV6\/RUNX1 or RUNX1\/MTG8, reduce adenovirus persistence in a B-lymphocyte line but do not dampen the initial acute infection phase. Further, we show that ETV6\/RUNX1 can bind to the viral genome and that some viral gene expression appears to be suppressed through the activities of HDACs in ETV6\/RUNX1-expressing cells. Finally, we show that the expression of virally silenced cellular genes remains repressed even after the loss of the virus from infected cells. The results of the current study provide support for how adenovirus could be lost from translocation containing lymphocytes and provide evidence that adenovirus can leave a lasting imprint on cells previously infected in the form of an epigenetic echo.\n                <\/jats:p>","DOI":"10.64898\/2025.12.19.695471","type":"posted-content","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T20:00:18Z","timestamp":1766520018000},"source":"Crossref","is-referenced-by-count":0,"title":["Leukemic fusion genes repress viral gene expression and expel adenovirus from persistently infected human B lymphocytes but evidence of the virus lingers behind"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5202-9564","authenticated-orcid":false,"given":"H. T.","family":"Wilms","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5151-8382","authenticated-orcid":false,"given":"D. 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