{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:13:12Z","timestamp":1753891992872,"version":"3.41.2"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>The lysine(K)-specific methyltransferase 2A gene (<jats:italic>KMT2A<\/jats:italic>), previously known as mixed lineage leukemia (<jats:italic>MLL<\/jats:italic>), frequently rearranged in acute leukemia, belongs to one of the most promiscuous genes and has been found fused to more than 80 different partners. <jats:italic>KMT2A<\/jats:italic>::<jats:italic>SEPTIN6<\/jats:italic> fusion is a relatively uncommon rearrangement observed in pediatric acute myeloid leukemia (AML) patients, some of which may harbor other mutations. We herein report a case of AML-M4-infant with <jats:italic>KMT2A<\/jats:italic>::<jats:italic>SEPTIN6<\/jats:italic> fusion and <jats:italic>DIS3<\/jats:italic> variant. The 8-month-old girl presented with leukocytosis, anemia and thrombocytopenia. A bone marrow smear disclosed that 64% of the total nucleated cells were blasts. Karyotype analysis showed 46,X,t(X;11)(q24;q23)[10]\/46,XX[10]. Fluorescence <jats:italic>in situ<\/jats:italic> hybridization analysis suggested a possible break in the <jats:italic>KMT2A<\/jats:italic> gene. After whole transcriptome sequencing, Exon 9 of <jats:italic>KMT2A<\/jats:italic> was fused in-frame with Exon 2 of <jats:italic>SEPTIN6<\/jats:italic>. This is a typical type of chromosomal rearrangement leading to the <jats:italic>KMT2A<\/jats:italic>::<jats:italic>SEPTIN6<\/jats:italic> fusion. Meanwhile, <jats:italic>DIS3<\/jats:italic> variant [c.2065C&amp;gt;T, p.R689X, variant allele frequency (VAF): 39.8%] was identified. <jats:italic>KMT2A<\/jats:italic>::<jats:italic>SEPTIN6<\/jats:italic> fusion has been associated with the pathogenesis of AML, whereas <jats:italic>DIS3<\/jats:italic> variants are relatively rare genetic events in pediatric AML. Regrettably, the relatives disagreed with the combination chemotherapy, and the patient eventually died of progressive disease. In conclusion, our findings provide a foundation for a better understanding of the genotypic profile of <jats:italic>KMT2A<\/jats:italic>::<jats:italic>SEPTIN6<\/jats:italic> associated AML, and the co-existence of <jats:italic>KMT2A<\/jats:italic>::<jats:italic>SEPTIN6<\/jats:italic> and <jats:italic>DIS3<\/jats:italic> variant might contribute to the disease progression and transformation of AML.<\/jats:p>","DOI":"10.3389\/fonc.2023.1308786","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T04:42:35Z","timestamp":1702442555000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Co-existence of KMT2A::SEPTIN6 fusion and DIS3 variant in a pediatric case with acute myeloid leukemia: a case report and literature review"],"prefix":"10.3389","volume":"13","author":[{"given":"Liang","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangzhou","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongming","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Si","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2005.01.007","article-title":"The versatile mixed lineage leukaemia gene MLL and its many associations in leukaemogenesis","volume":"15","author":"Daser","year":"2005","journal-title":"Semin Cancer Biol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1038\/s41375-023-01877-1","article-title":"The KMT2A recombinome of acute leukemias in 2023","volume":"37","author":"Meyer","year":"2023","journal-title":"Leukemia"},{"key":"B3","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3892\/ijo.2021.5205","article-title":"SEPT6 drives hepatocellular carcinoma cell proliferation, migration and invasion via the Hippo\/YAP signaling pathway","volume":"58","author":"Fan","year":"2021","journal-title":"Int J Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.lrr.2021.100277","article-title":"Pediatric M5 acute myeloid leukemia with MLL-SEPT6 fusion and a favorable outcome","volume":"16","author":"Chebly","year":"2021","journal-title":"Leuk Res Rep"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/biom5031515","article-title":"The 3\u2019 to 5\u2019 Exoribonuclease DIS3: from structure and mechanisms to biological functions and role in human disease","volume":"5","author":"Robinson","year":"2015","journal-title":"Biomolecules"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nature10738","article-title":"Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing","volume":"481","author":"Ding","year":"2012","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1182\/blood-2019-123352","article-title":"DIS3 mutation in RUNX1-mutated AML1 confers a highly dismal prognosis in AML by repressing sister chromatid cohesion","volume":"134","author":"Desterke","year":"2019","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.jmoldx.2016.10.002","article-title":"Standards and guidelines for the interpretation and reporting of sequence variants in cancer: A joint consensus recommendation of the association for molecular pathology, american society of clinical oncology, and college of american pathologists","volume":"19","author":"Li","year":"2017","journal-title":"J Mol Diagn"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401017","article-title":"Ten novel 11q23 chromosomal partner sites. 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