title: Differential expression of AURKA and AURKB genes in bone marrow stromal mesenchymal cells of myelodysplastic syndrome: correlation with G-banding analysis and FISH.
abstract: It has been demonstrated that genomic alterations of cells in the hematopoietic microenvironment could induce myelodysplastic syndromes (MDS) with ineffective hematopoiesis and dysmorphic hematopoietic cells, and subsequent transformation to acute myeloid leukemia. This investigation is the first attempt to correlate the gene expression profile of AURKA and AURKB in a cytogenetically stratified population of mesenchymal stem cells (MSCs) from MDS patients. We found that AURKA messenger RNA was expressed at significantly higher levels in MSCs even with normal/altered karyotype when compared with hematopoietic cells and healthy donors. In addition, we found that the presence of chromosomal abnormalities (mainly aneuploidy) in hematopoietic cells/MSCs was also associated with higher levels of AURKA. Different from previous investigations, our findings, regarding AURKA expression support the hypothesis that the presence of chromosomal abnormalities in MSCs from MDS is not a consequence of the method used for chromosome preparation. They may reflect the genomic instability present in the bone marrow microenvironment of MDS patients. This information is also supported by differences observed in the growth kinetics between MSCs from healthy donors (normal karyotype) and from MDS patients with abnormal karyotype. In summary, our results may not be considered evidence that MDS and MSCs are originated from a single neoplastic clone. In fact, both cells (hematopoietic and MSCs) may probably be altered in response to damage-inducing factors, and the presence of genomic abnormalities in MSCs suggests that an unstable bone marrow microenvironment may facilitate the expansion of MDS/leukemic cells.
authors.affiliation: Department of Internal Medicine, Division of Hematology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes 3900, São Paulo, Brazil. morato.oliveira@yahoo.com.br
authors.forename: Fábio Morato de
authors.initials: FM
authors.lastname: Oliveira
authors.forename: Antonio Roberto
authors.initials: AR
authors.lastname: Lucena-Araujo
authors.forename: Maria do Carmo
authors.initials: Mdo C
authors.lastname: Favarin
authors.forename: Patrícia Vianna Bonini
authors.initials: PV
authors.lastname: Palma
authors.forename: Eduardo Magalhães
authors.initials: EM
authors.lastname: Rego
authors.forename: Roberto Passetto
authors.initials: RP
authors.lastname: Falcão
authors.forename: Dimas Tadeu
authors.initials: DT
authors.lastname: Covas
authors.forename: Aparecida Maria
authors.initials: AM
authors.lastname: Fontes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D001854:Bone Marrow Cells / Q000201:enzymology*; D002478:Cells, Cultured / Q000201:enzymology; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D004790:Enzyme Induction; D005260:Female; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000201:enzymology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D008297:Male; D059630:Mesenchymal Stem Cells / Q000201:enzymology*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D055153:Stem Cell Niche
chemical_list: D012333:RNA, Messenger; C576917:AURKA protein, human; C576921:AURKB protein, human; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases