{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:15:18Z","timestamp":1790972118896,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,3,18]],"date-time":"2005-03-18T00:00:00Z","timestamp":1111104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2005,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The mixed lineage leukemia (<jats:italic>MLL<\/jats:italic>) gene encodes a very large nuclear protein homologous to <jats:italic>Drosophila<\/jats:italic> trithorax (trx). MLL is required for the proper maintenance of <jats:italic>HOX<\/jats:italic> gene expression during development and hematopoiesis. The exact regulatory mechanism of <jats:italic>HOX<\/jats:italic> gene expression by MLL is poorly understood, but it is believed that MLL functions at the level of chromatin organization. <jats:italic>MLL<\/jats:italic> was identified as a common target of chromosomal translocations associated with human acute leukemias. About 50 different MLL fusion partners have been isolated to date, and while similarities exist between groups of partners, there exists no unifying property shared by all the partners. <jats:italic>MLL<\/jats:italic> gene rearrangements are found in leukemias with both lymphoid and myeloid phenotypes and are often associated with infant and secondary leukemias. The immature phenotype of the leukemic blasts suggests an important role for MLL in the early stages of hematopoietic development. <jats:italic>Mll<\/jats:italic> homozygous mutant mice are embryonic lethal and exibit deficiencies in yolk sac hematopoiesis. Recently, two different MLL\u2010containing protein complexes have been isolated. These and other gain\u2010 and loss\u2010of\u2010function experiments have provided insight into normal MLL function and altered functions of MLL fusion proteins. This article reviews the progress made toward understanding the function of the wild\u2010type MLL protein. While many advances in understanding this multifaceted protein have been made since its discovery, many challenging questions remain to be answered. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.20430","type":"journal-article","created":{"date-parts":[[2005,3,19]],"date-time":"2005-03-19T12:26:07Z","timestamp":1111235167000},"page":"234-242","source":"Crossref","is-referenced-by-count":74,"title":["MLL: How complex does it get?"],"prefix":"10.1002","volume":"95","author":[{"given":"Relja","family":"Popovic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy 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