title: Expression pattern of the septin gene family in acute myeloid leukemias with and without MLL-SEPT fusion genes.
abstract: Septins are proteins associated with crucial steps in cell division and cellular integrity. In humans, 14 septin genes have been identified, of which five (SEPT2, SEPT5, SEPT6, SEPT9, and SEPT11) are known to participate in reciprocal translocations with the MLL gene in myeloid neoplasias. We have recently shown a significant down-regulation of both SEPT2 and MLL in myeloid neoplasias with the MLL-SEPT2 fusion gene. In this study, we examined the expression pattern of the other 13 known septin genes in altogether 67 cases of myeloid neoplasia, including three patients with the MLL-SEPT2 fusion gene, four with MLL-SEPT6 fusion, and three patients with the MLL-SEPT9 fusion gene. When compared with normal controls, a statistically significant down-regulation was observed for the expression of both MLL (6.4-fold; p=0.008) and SEPT6 (1.7-fold; p=0.002) in MLL-SEPT6 leukemia. Significant down-regulation of MLL was also found in MLL-MLLT3 leukemias. In addition, there was a trend for SEPT9 down-regulation in MLL-SEPT9 leukemias (4.6-fold; p=0.077). Using hierarchical clustering analysis to compare acute myeloid leukemia genetic subgroups based on their similarity of septin expression changes, we found that MLL-SEPT2 and MLL-SEPT6 neoplasias cluster together apart from the remaining subgroups and that PML-RARA leukemia presents under-expression of most septin family genes.
authors.affiliation: Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Santos
authors.forename: Nuno
authors.initials: N
authors.lastname: Cerveira
authors.forename: Susana
authors.initials: S
authors.lastname: Bizarro
authors.forename: Franclim R
authors.initials: FR
authors.lastname: Ribeiro
authors.forename: Cecília
authors.initials: C
authors.lastname: Correia
authors.forename: Lurdes
authors.initials: L
authors.lastname: Torres
authors.forename: Susana
authors.initials: S
authors.lastname: Lisboa
authors.forename: Joana
authors.initials: J
authors.lastname: Vieira
authors.forename: José M
authors.initials: JM
authors.lastname: Mariz
authors.forename: Lucília
authors.initials: L
authors.lastname: Norton
authors.forename: Simone
authors.initials: S
authors.lastname: Snijder
authors.forename: Clemens H
authors.initials: CH
authors.lastname: Mellink
authors.forename: Arjan
authors.initials: A
authors.lastname: Buijs
authors.forename: Lee-Yung
authors.initials: LY
authors.lastname: Shih
authors.forename: Sabine
authors.initials: S
authors.lastname: Strehl
authors.forename: Francesca
authors.initials: F
authors.lastname: Micci
authors.forename: Sverre
authors.initials: S
authors.lastname: Heim
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D003598:Cytoskeletal Proteins / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D003598:Cytoskeletal Proteins; C512503:MLL-SEPT6 fusion protein, human; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein; D019204:GTP-Binding Proteins