{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:25:24Z","timestamp":1785799524399,"version":"3.56.0"},"reference-count":84,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Leukemias derived from the MLL-AF9 rearrangement rely on dysfunctional transcriptional networks. ZNF521, a transcription co-factor implicated in the control of hematopoiesis, has been proposed to sustain leukemic transformation in collaboration with other oncogenes. Here, we demonstrate that ZNF521 mRNA levels correlate with specific genetic aberrations: in particular, the highest expression is observed in AMLs bearing MLL rearrangements, while the lowest is detected in AMLs with FLT3-ITD, NPM1, or CEBP\u03b1 double mutations. In cord blood-derived CD34+ cells, enforced expression of ZNF521 provides a significant proliferative advantage and enhances MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome analysis of primary CD34+ cultures displayed subsets of genes up-regulated by MLL-AF9 or ZNF521 single transgene overexpression as well as in MLL-AF9\/ZNF521 combinations, at either the early or late time points of an in vitro leukemogenesis model. The silencing of ZNF521 in the MLL-AF9 + THP-1 cell line coherently results in an impairment of growth and clonogenicity, recapitulating the effects observed in primary cells. Taken together, these results underscore a role for ZNF521 in sustaining the self-renewal of the immature AML compartment, most likely through the perturbation of the gene expression landscape, which ultimately favors the expansion of MLL-AF9-transformed leukemic clones.<\/jats:p>","DOI":"10.3390\/ijms221910814","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T16:23:58Z","timestamp":1633623838000},"page":"10814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["ZNF521 Enhances MLL-AF9-Dependent Hematopoietic Stem Cell Transformation in Acute Myeloid Leukemias by Altering the Gene Expression Landscape"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8314-715X","authenticated-orcid":false,"given":"Emanuela","family":"Chiarella","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University Magna Gr\u00e6cia, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Aloisio","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University Magna Gr\u00e6cia, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3566-7214","authenticated-orcid":false,"given":"Stefania","family":"Scicchitano","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University Magna Gr\u00e6cia, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Todoerti","sequence":"additional","affiliation":[{"name":"Hematology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3611-5649","authenticated-orcid":false,"given":"Emanuela G.","family":"Cosentino","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University Magna Gr\u00e6cia, 88100 Catanzaro, Italy"},{"name":"Exiris S.r.l., 00128 Roma, Italy"},{"name":"Department of Hematology, Cancer Research Centre Groningen, University Medical Centre Groningen, University of Groningen, 9712 CP Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Lico","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Pugliese-Ciaccio Hospital, University Magna Gr\u00e6cia, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Neri","sequence":"additional","affiliation":[{"name":"Hematology, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Amodio","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University Magna Gr\u00e6cia, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4033-2985","authenticated-orcid":false,"given":"Heather Mandy","family":"Bond","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University Magna Gr\u00e6cia, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5455-168X","authenticated-orcid":false,"given":"Maria","family":"Mesuraca","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University Magna 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