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Among the most common genomic alterations,<jats:italic>CBFB-MYH11<\/jats:italic>rearrangement and<jats:italic>FLT3<\/jats:italic>-ITD gene mutations, have opposite clinical significance and are unfrequently associated. We present here a Molecular Case Report in which these two events co-exist an ultra-aggressive phenotype resulting in death in 4\u00a0days from hospital admittance. Somatic and germline Whole Exome Sequencing analysis was performed to uncover other putative driver mutations, de-novo genomic structural events or germline clusters increasing cancer insurgence. Only three mutations in<jats:italic>LTK<\/jats:italic>,<jats:italic>BCAS2<\/jats:italic>and<jats:italic>LGAS9<\/jats:italic>were found, unlikely causative of the exhibited phenotype, prompting to additional investigation of the rare<jats:italic>CBFB-MYH11\/ FLT3-<\/jats:italic>ITD scenario.<\/jats:p>","DOI":"10.1186\/s12967-022-03486-5","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T09:02:58Z","timestamp":1657098178000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular dissection of a hyper-aggressive CBFB-MYH11\/FLT3-ITD\u2013positive acute myeloid leukemia"],"prefix":"10.1186","volume":"20","author":[{"given":"Gabriele","family":"Lo Iudice","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"De Bellis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arianna","family":"Savi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Guarnera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Massacci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"De Nicola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frauke","family":"Goeman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziana","family":"Ottone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariadomenica","family":"Divona","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7756-3579","authenticated-orcid":false,"given":"Matteo","family":"Pallocca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Fanciulli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Teresa","family":"Voso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gennaro","family":"Ciliberto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"issue":"10","key":"3486_CR1","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.1038\/s41375-018-0071-7","volume":"32","author":"M Rasche","year":"2018","unstructured":"Rasche M, Zimmermann M, Borschel L, et al. 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