{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:24:43Z","timestamp":1790637883371,"version":"4.1.0"},"reference-count":39,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,4,7]]},"abstract":"<jats:p>Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) exhibits lymphoid, myeloid, and stem cell features and is associated with a poor prognosis. Whole genome sequencing of human ETP-ALL cases has identified recurrent mutations in signaling, histone modification, and hematopoietic development genes but it remains to be determined which of these abnormalities are sufficient to initiate leukemia. We show that activating mutations in the interleukin-7 receptor identified in human pediatric ETP-ALL cases are sufficient to generate ETP-ALL in mice transplanted with primitive transduced thymocytes from p19Arf\u2212\/\u2212 mice. The cellular mechanism by which these mutant receptors induce ETP-ALL is the block of thymocyte differentiation at the double negative 2 stage at which myeloid lineage and T lymphocyte developmental potential coexist. Analyses of samples from pediatric ETP-ALL cases and our murine ETP-ALL model show uniformly high levels of LMO2 expression, very low to undetectable levels of BCL11B expression, and a relative lack of activating NOTCH1 mutations. We report that pharmacological blockade of Jak\u2013Stat signaling with ruxolitinib has significant antileukemic activity in this ETP-ALL model. This new murine model recapitulates several important cellular and molecular features of ETP-ALL and should be useful to further define novel therapeutic approaches for this aggressive leukemia.<\/jats:p>","DOI":"10.1084\/jem.20122727","type":"journal-article","created":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T01:27:25Z","timestamp":1396315645000},"page":"701-713","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":93,"title":["Interleukin-7 receptor mutants initiate early T cell precursor leukemia in murine thymocyte progenitors with multipotent potential"],"prefix":"10.1084","volume":"211","author":[{"given":"Louise M.","family":"Treanor","sequence":"first","affiliation":[{"name":"Department of Hematology 1 and 2"},{"name":"Department of Pathology, Division of Experimental Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Hematology 1 and 2"},{"name":"Department of Pathology, Division of Experimental Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Janke","sequence":"additional","affiliation":[{"name":"Department of Hematology 1 and 2"},{"name":"Department of Pathology, Division of Experimental Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Churchman","sequence":"additional","affiliation":[{"name":"Department of Hematology 1 and 2"},{"name":"Department of Pathology, Division of Experimental Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Hematology 1 and 2"},{"name":"Department of Pathology, Division of Experimental Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taihe","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Hematology 1 and 2"},{"name":"Department of Pathology, Division of Experimental Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shann-Ching","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hematology 1 and 2"},{"name":"Department of Pathology, Division of Experimental Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles G.","family":"Mullighan","sequence":"additional","affiliation":[{"name":"Department of Hematology 1 and 2"},{"name":"Department of Pathology, Division of Experimental Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P.","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"Department of Hematology 1 and 2"},{"name":"Department of Pathology, Division of Experimental Hematology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2014,3,31]]},"reference":[{"key":"2023072602121493400_bib1","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1038\/nature06840","article-title":"The earliest thymic progenitors for T cells possess myeloid lineage potential","volume":"452","author":"Bell","year":"2008","journal-title":"Nature."},{"key":"2023072602121493400_bib2","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/S1470-2045(08)70314-0","article-title":"Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia","volume":"10","author":"Coustan-Smith","year":"2009","journal-title":"Lancet Oncol."},{"key":"2023072602121493400_bib3","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1182\/blood-2012-08-451773","article-title":"Early T-cell progenitors are the major granulocyte precursors in the adult mouse thymus","volume":"121","author":"De Obaldia","year":"2013","journal-title":"Blood."},{"key":"2023072602121493400_bib4","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1038\/nm.2415","article-title":"Stem cell gene expression programs influence clinical outcome in human leukemia","volume":"17","author":"Eppert","year":"2011","journal-title":"Nat. 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