Department of Internal Medicine, Division of Hematology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes 3900, São Paulo, Brazil.
Exp Hematol. 2013 Feb;41(2):198-208. doi: 10.1016/j.exphem.2012.10.009. Epub 2012 Oct 22.
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.
已有研究表明,造血微环境中细胞的基因组改变可导致无效造血和形态异常的造血细胞,并随后转化为急性髓系白血病。本研究首次尝试将 AURKA 和 AURKB 的基因表达谱与 MDS 患者间充质干细胞(MSC)的细胞遗传学分层人群相关联。我们发现,与造血细胞和健康供体相比,AURKA 信使 RNA 在 MSC 中表达水平显著更高,即使核型正常/改变也是如此。此外,我们发现造血细胞/MSC 中存在染色体异常(主要是非整倍体)也与 AURKA 水平升高相关。与先前的研究不同,我们关于 AURKA 表达的发现支持这样的假设,即 MDS 中 MSC 存在染色体异常不是染色体制备方法所致。它们可能反映了 MDS 患者骨髓微环境中存在的基因组不稳定性。这一信息也得到了健康供体(正常核型)和 MDS 患者(异常核型)间 MSC 生长动力学差异的支持。总之,我们的结果可能不能被视为 MDS 和 MSC 来源于单个肿瘤克隆的证据。事实上,这两种细胞(造血细胞和 MSC)可能都因诱导损伤的因素而发生改变,并且 MSC 中存在基因组异常表明不稳定的骨髓微环境可能促进 MDS/白血病细胞的扩增。