{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:56:36Z","timestamp":1791114996387,"version":"4.1.0"},"reference-count":49,"publisher":"Cold Spring Harbor Laboratory","issue":"18","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[2003,9,15]]},"abstract":"<jats:p>Transcriptional deregulation through the production of dominant-acting chimeric transcription factors derived from chromosomal translocations is a common theme in the pathogenesis of acute leukemias; however, the essential target genes for acute leukemogenesis are unknown. We demonstrate here that primary myeloid progenitors immortalized by various MLL oncoproteins exhibit a characteristic <jats:italic>Hoxa<\/jats:italic> gene cluster expression profile, which reflects that preferentially expressed in the myeloid clonogenic progenitor fraction of normal bone marrow. Continued maintenance of this MLL-dependent <jats:italic>Hoxa<\/jats:italic> gene expression profile is associated with conditional MLL-associated myeloid immortalization. Moreover, <jats:italic>Hoxa7<\/jats:italic> and <jats:italic>Hoxa9<\/jats:italic> were specifically required for efficient in vitro myeloid immortalization by an MLL fusion protein but not other leukemogenic fusion proteins. Finally, in a bone marrow transduction\/transplantation model, <jats:italic>Hoxa9<\/jats:italic> is essential for MLL-dependent leukemogenesis in vivo, a primary requirement detected at the earliest stages of disease initiation. Thus, a genetic reliance on <jats:italic>Hoxa7<\/jats:italic> and <jats:italic>Hoxa9<\/jats:italic> in <jats:italic>MLL<\/jats:italic>-mediated transformation demonstrates a gain-of-function mechanism for MLL oncoproteins as upstream constitutive activators that promote myeloid transformation via a <jats:italic>Hox<\/jats:italic>-dependent mechanism.<\/jats:p>","DOI":"10.1101\/gad.1111603","type":"journal-article","created":{"date-parts":[[2003,9,9]],"date-time":"2003-09-09T02:20:46Z","timestamp":1063074046000},"page":"2298-2307","source":"Crossref","is-referenced-by-count":394,"title":["Transformation of myeloid progenitors by MLL oncoproteins is dependent on <i>Hoxa7<\/i> and <i>Hoxa9<\/i>"],"prefix":"10.1101","volume":"17","author":[{"given":"Paul M.","family":"Ayton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Cleary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2003,1,1]]},"reference":[{"key":"2021111519304524000_17.18.2298.1","doi-asserted-by":"publisher","DOI":"10.1038\/ng765"},{"key":"2021111519304524000_17.18.2298.2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204639"},{"key":"2021111519304524000_17.18.2298.3","doi-asserted-by":"publisher","DOI":"10.1002\/gene.1066"},{"key":"2021111519304524000_17.18.2298.4","first-page":"301","volume":"71","year":"2000","journal-title":"Int. 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