Expression pattern of the septin gene family in acute myeloid leukemias with and without MLL-SEPT fusion genes.
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.
Santos
Joana
J
Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
Cerveira
Nuno
N
Bizarro
Susana
S
Ribeiro
Franclim R
FR
Correia
Cecília
C
Torres
Lurdes
L
Lisboa
Susana
S
Vieira
Joana
J
Mariz
José M
JM
Norton
Lucília
L
Snijder
Simone
S
Mellink
Clemens H
CH
Buijs
Arjan
A
Shih
Lee-Yung
LY
Strehl
Sabine
S
Micci
Francesca
F
Heim
Sverre
S
Teixeira
Manuel R
MR
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
D003598:Cytoskeletal Proteins; C512503:MLL-SEPT6 fusion protein, human; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein; D019204:GTP-Binding Proteins