{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:24:52Z","timestamp":1768505092091,"version":"3.49.0"},"posted":{"date-parts":[[2023,4,25]]},"group-title":"Cancer Biology","reference-count":62,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,4,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  T lymphocyte acute lymphoblastic leukemia (T-ALL) is frequently associated with increased expression of the E protein transcription factor inhibitors TAL1 and LYL1. In mouse models, ectopic expression of Tal1 or Lyl1 in T cell progenitors or inactivation of E2a, is sufficient to predispose mice to develop T-ALL. How E2a suppresses thymocyte transformation is currently unknown. Here, we show that early deletion of\n                  <jats:italic>E2a<\/jats:italic>\n                  , prior to the DN3 stage, was required for robust leukemogenesis and was associated with alterations in thymus cellularity, T cell differentiation, and gene expression in immature CD4+CD8+ thymocytes. Introduction of wild-type thymocytes into mice with early deletion of\n                  <jats:italic>E2a<\/jats:italic>\n                  prevented leukemogenesis, or delayed disease onset, and impacted the expression of multiple genes associated with transformation and genome instability. Our data indicate that E2a suppresses leukemogenesis by promoting T cell development and enforcing inter-thymocyte competition, a mechanism that is emerging as a safeguard against thymocyte transformation. These studies have implications for understanding how multiple essential regulators of T cell development suppress T-ALL and support the hypothesis that thymus cellularity is a determinant of leukemogenesis.\n                <\/jats:p>","DOI":"10.1101\/2023.04.23.537993","type":"posted-content","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T18:35:15Z","timestamp":1682447715000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss of thymocyte competition underlies the tumor suppressive functions of the E2a transcription factor in T lymphocyte acute lymphoblastic leukemia"],"prefix":"10.64898","author":[{"given":"Geoffrey","family":"Parriott","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Hegermiller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosemary 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