title: SEPTIN6, a human homologue to mouse Septin6, is fused to MLL in infant acute myeloid leukemia with complex chromosomal abnormalities involving 11q23 and Xq24.
abstract: t(X;11) is a recurrent translocation in pediatric acute myeloid leukemia (AML). We showed that the MLL gene on 11q23 was fused to the SEPTIN6 gene on Xq24, a human homologue to mouse Septin6, in three de novo infant AML with complex chromosomal abnormalities involving 11q23 and Xq22-24. SEPTIN6 consisted of at least 12 exons and was predicted to encode at least two types of proteins by alternative splicing. Expression of approximately 2.3-, 3.1-, and 4.6-kb SEPTIN6 transcripts was simultaneously detected in fetal lung, liver, and brain, in all of the adult tissues except brain, and in acute lymphoblastic leukemia and AML cell lines. However, the expression of an approximately 2.7-kb transcript was detected alone in fetal heart and adult brain. The SEPTIN6 protein is homologous to septin family members including CDCREL1 and AF17q25/MSF, which generate fusion products with MLL. The MLL-SEPTIN6 fusion proteins contain almost the entire septin protein, similar to MLL-CDCREL1 and MLL-AF17q25/MSF. Notably, all three of the patients were diagnosed with M1 or M2. Combined present results and literatures suggest that AML with the MLL-SEPTIN6 fusion gene is a subset of infant AML, which differentiate into the myeloid lineage, although AML with other MLL fusion genes is capable of differentiating into the myelomonocytic or monocytic lineage.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Ono
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Taki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Taketani
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Okamura
authors.forename: Keisei
authors.initials: K
authors.lastname: Kawa
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hanada
authors.forename: Miyuki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000328:Adult; D000818:Animals; D019677:Artificial Gene Fusion; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D051788:Myeloid-Lymphoid Leukemia Protein; D011519:Proto-Oncogenes; D058112:Septins; D014157:Transcription Factors; D014178:Translocation, Genetic; D014960:X Chromosome
chemical_list: D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497423:Kmt2a protein, mouse; D019204:GTP-Binding Proteins; C436485:SEPTIN6 protein, human; C486672:Sept6 protein, mouse; D058112:Septins