{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:04:23Z","timestamp":1789016663261,"version":"build-2803163510"},"reference-count":0,"publisher":"American Society of Hematology","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Acute leukemias (AL) of ambiguous lineage are a heterogeneous group of high-risk leukemias characterized by co-expression of myeloid and lymphoid markers. In this study, we identified a distinct subgroup of immature acute leukemias characterized by a broadly variable phenotype, covering acute myeloid leukemia (AML M0 or M1), T\/myeloid mixed phenotype acute leukemia (T\/M MPAL), and early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Rearrangements at 14q32\/BCL11B are the cytogenetic hallmark of this entity. In our screening of 915 hematological malignancies, there were 202 AML and 333 T-cell Acute Lymphoblastic Leukemia (T-ALL) (58 ETP, 178 non-ETP, 8 T\/M MPAL, 89 not otherwise specified). We identified 20 cases of immature leukemias (4% of AML and 3,6% of T-ALL) harbouring four types of 14q32\/BCL11B translocations: t(2,14)(q22.3;q32) (n=7), t(6;14)(q25.3;q32) (n=9), t(7;14)(q21.2;q32) (n=2) and t(8;14)(q24.2;q32) (n=2). The t(2;14) produced a ZEB2-BCL11B fusion transcript, while the other three rearrangements displaced transcriptionally active enhancer sequences close to BCL11B without producing fusion genes. All translocations resulted in the activation of BCL11B, a regulator of T-cell differentiation associated with transcriptional corepressor complexes in mammalian cells. The expression of BCL11B behaved as a disease biomarker, which was present at diagnosis but not in remission. Deregulation of BCL11B co-occurred with variants at FLT3 and at epigenetic modulators, most frequently DNMT3A, TET2 and\/or WT1 gene. Transcriptome analysis identified a specific expression signature, with significant downregulation of BCL11B targets, and clearly separating BCL11B positive AL from AML, T-ALL, and ETP-ALL. Remarkably, ex-vivo drug sensitivity profile identified a panel of compounds with effective antileukemic activity.<\/jats:p>","DOI":"10.1182\/blood.2020010510","type":"journal-article","created":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T06:44:19Z","timestamp":1618901059000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":17,"title":["14q32 rearrangements deregulating <i>BCL11B <\/i>mark a distinct subgroup of T and myeloid immature acute leukemia"],"prefix":"10.1182","author":[{"given":"Danika","family":"Di Giacomo","sequence":"first","affiliation":[{"name":"University of Perugia, Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"La Starza","sequence":"additional","affiliation":[{"name":"University of Perugia, Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Gorello","sequence":"additional","affiliation":[{"name":"University of Perugia, Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizia","family":"Pellanera","sequence":"additional","affiliation":[{"name":"Hematology and Bone Marrow Transplantation, University of Perugia, Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4761-8169","authenticated-orcid":false,"given":"Zeynep","family":"Kalender Atak","sequence":"additional","affiliation":[{"name":"Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge UK, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7420-9531","authenticated-orcid":false,"given":"Kim","family":"De Keersmaecker","sequence":"additional","affiliation":[{"name":"KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Pierini","sequence":"additional","affiliation":[{"name":"University of Perugia, Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine J","family":"Harrison","sequence":"additional","affiliation":[{"name":"Newcastle University, Newcastle-upon-Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Arniani","sequence":"additional","affiliation":[{"name":"University of Perugia, Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Moretti","sequence":"additional","affiliation":[{"name":"University of Perugia, Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Testoni","sequence":"additional","affiliation":[{"name":"University of Bologna \"Seragnoli\", Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"De Santis","sequence":"additional","affiliation":[{"name":"6U.O.C. of Hematology, Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Roti","sequence":"additional","affiliation":[{"name":"University of Parma, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9553-4819","authenticated-orcid":false,"given":"Caterina","family":"Matteucci","sequence":"additional","affiliation":[{"name":"University of Perugia, Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Bassan","sequence":"additional","affiliation":[{"name":"Ospedale dell'Angelo, Mestre-Venezia, Mestre-Venezia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4719-1935","authenticated-orcid":false,"given":"Peter","family":"Vandenberghe","sequence":"additional","affiliation":[{"name":"University Hospital Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stein","family":"Aerts","sequence":"additional","affiliation":[{"name":"VIB Center for Brain & Disease Research, Leuven, Belgium, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6626-5843","authenticated-orcid":false,"given":"Jan","family":"Cools","sequence":"additional","affiliation":[{"name":"KU Leuven - VIB, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beat","family":"Bornhauser","sequence":"additional","affiliation":[{"name":"University Childrens Hospital, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Bourquin","sequence":"additional","affiliation":[{"name":"Universitaets-Kinderklinik Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4198-9620","authenticated-orcid":false,"given":"Rocco","family":"Piazza","sequence":"additional","affiliation":[{"name":"University of Milano - Bicocca, Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1623-0148","authenticated-orcid":false,"given":"Cristina","family":"Mecucci","sequence":"additional","affiliation":[{"name":"University of Perugia, Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2021,4,19]]},"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2020010510\/1805715\/blood.2020010510.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/doi\/10.1182\/blood.2020010510\/1805715\/blood.2020010510.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T06:44:19Z","timestamp":1618901059000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/doi\/10.1182\/blood.2020010510\/475778\/14q32-rearrangements-deregulating-BCL11B-mark-a"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,19]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1182\/blood.2020010510","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,19]]},"article-number":"blood.2020010510"}}