title: High expression of the sister-chromatid separation regulator and proto-oncogene hSecurin occurs in a subset of myeloid leukaemias but is not implicated in the pathogenesis of aneuploidy.
abstract: Aneuploidy is considered to play an important role in the pathogenesis of malignancies. We were interested whether abnormalities of the sister-chromatid separation regulator and proto-oncogene hSecurin occurred in myeloid leukaemias, and whether such abnormalities correlated with aneuploidy. The expression of hSecurin was assessed by real-time quantitative PCR in samples from patients with acute myeloid leukaemia (AML, n=70), chronic myeloid leukaemia (CML) in chronic phase (CP, n=20) or blast phase (BP, n=12), and granulocytes as well as mononuclear cells (MNCs) from healthy donors (n=21). Median hSecurin expression in AML with normal karyotypes was not significantly different from AML showing aneuploidy, CML BP or cells from healthy donors. However, hSecurin expression in CML CP was significantly increased compared to AML with normal karyotypes (1.82-fold; P<0.001), CML BP (3.18-fold; P<0.001), MNCs (3.17-fold; P<0.001) and granulocytes (2.69 fold; P<0.001) from healthy donors. Mutations in the coding region of hSecurin were not detected. These results do not support a major role of hSecurin in the development of aneuploidy in myeloid leukaemias. However, high expression of hSecurin may be of pathogenetic relevance in a subset of patients with regard to its potential to stimulate angiogenesis and to interact with the DNA-damage response pathway.
authors.affiliation: Division of Haematology, Karl-Franzens University, Graz, Austria.
authors.forename: H W
authors.initials: HW
authors.lastname: Auner
authors.forename: A
authors.initials: A
authors.lastname: Zebisch
authors.forename: M G
authors.initials: MG
authors.lastname: Schimek
authors.forename: C
authors.initials: C
authors.lastname: Bodner
authors.forename: K
authors.initials: K
authors.lastname: Hiden
authors.forename: W
authors.initials: W
authors.lastname: Linkesch
authors.forename: O A
authors.initials: OA
authors.lastname: Haas
authors.forename: C
authors.initials: C
authors.lastname: Beham-Schmid
authors.forename: H
authors.initials: H
authors.lastname: Sill
mesh_terms: D000208:Acute Disease; D000782:Aneuploidy; D016022:Case-Control Studies; D002842:Chromatids; D002908:Chronic Disease; D020732:Cytogenetic Analysis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007951:Leukemia, Myeloid / Q000145:classification / Q000473:pathology*; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D064249:Securin; D017422:Sequence Analysis, DNA
chemical_list: C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D064249:Securin