title: Disruption of Sept6, a fusion partner gene of MLL, does not affect ontogeny, leukemogenesis induced by MLL-SEPT6, or phenotype induced by the loss of Sept4.
abstract: Septins are evolutionarily conserved GTP-binding proteins that can heteropolymerize into filaments. Recent studies have revealed that septins are involved in not only diverse normal cellular processes but also the pathogenesis of various diseases, including cancer. SEPT6 is ubiquitously expressed in tissues and one of the fusion partner genes of MLL in the 11q23 translocations implicated in acute leukemia. However, the roles of this septin in vivo remain elusive. We have developed Sept6-deficient mice that exhibited neither gross abnormalities, changes in cytokinesis, nor spontaneous malignancy. Sept6 deficiency did not cause any quantitative changes in any of the septins evaluated in this study, nor did it cause any additional changes in the Sept4-deficient mice. Even the depletion of Sept11, a close homolog of Sept6, did not affect the Sept6-null cells in vitro, thus implying a high degree of redundancy in the septin system. Furthermore, a loss of Sept6 did not alter the phenotype of myeloproliferative disease induced by MLL-SEPT6, thus suggesting that Sept6 does not function as a tumor suppressor. To our knowledge, this is the first report demonstrating that a disruption of the translocation partner gene of MLL in 11q23 translocation does not contribute to leukemogenesis by the MLL fusion gene.
authors.affiliation: Division of Hematopoietic Factors, The Institute of Medical Science, The University of Tokyo, Minato-ku, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Ono
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Ozaki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kataoka-Fujiwara
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Taki
authors.forename: Koh-Ichi
authors.initials: K
authors.lastname: Nagata
authors.forename: Masaki
authors.initials: M
authors.lastname: Inagaki
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Yoshida
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitamura
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nosaka
mesh_terms: D000818:Animals; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000172:deficiency / Q000235:genetics; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000473:pathology; D011495:Histone-Lysine N-Methyltransferase; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010641:Phenotype; D058112:Septins; D014178:Translocation, Genetic
chemical_list: D003598:Cytoskeletal Proteins; C507324:MLL-SEPT6 fusion protein, mouse; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497423:Kmt2a protein, mouse; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C115474:Sept4 protein, mouse; C486672:Sept6 protein, mouse; D058112:Septins