Differential expression of AURKA and AURKB genes in bone marrow stromal mesenchymal cells of myelodysplastic syndrome: correlation with G-banding analysis and FISH

Autor(es)

de Oliveira, Fabio Morato ^{[1, 2]} ; Lucena-Araujo, Antonio Roberto ^{[1, 2]} ; Favarin, Maria do Carmo ^[1] ; Bonini Palma, Patricia Vianna ^[2] ; Rego, Eduardo Magalhaes ^{[1, 2]} ; Falcao, Roberto Passetto ^{[1, 2]} ; Covas, Dimas Tadeu ^{[1, 2]} ; Fontes, Aparecida Maria ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Div Hematol, Dept Internal Med, BR-14049900 Sao Paulo - Brazil

^[2] Natl Inst Sci & Technol Stem Cell & Cell Therapy, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Hematology; v. 41, n. 2, p. 198-208, FEB 2013.
• Citações Web of Science: 16

Resumo

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. (C) 2013 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. (AU)

• Processo FAPESP: 07/52462-7 - Citogenética clássica e cariótipo espectral (SKY) aplicados à caracterização da leucemia linfocítica crônica B (LLC-B) imunoestimulada pelo oligonucleotídeo DSP30 e IL-2
• Beneficiário: Fábio Morato de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/01647-2 - Avaliação da instabilidade genômica, por meio da organização tridimensional nuclear de telômeros, na sindrome mielodisplásica (SMD)
• Beneficiário: Fábio Morato de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores