Garayoa M, Garcia J L, Santamaria C, Garcia-Gomez A, Blanco J F, Pandiella A, Hernández J M, Sanchez-Guijo F M, del Cañizo M-C, Gutiérrez N C, San Miguel J F
Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Universidad de Salamanca-CSIC, Salamanca, Spain.
Leukemia. 2009 Aug;23(8):1515-27. doi: 10.1038/leu.2009.65. Epub 2009 Apr 9.
It is an open question whether in multiple myeloma (MM) bone marrow stromal cells contain genomic alterations, which may contribute to the pathogenesis of the disease. We conducted an array-based comparative genomic hybridization (array-CGH) analysis to compare the extent of unbalanced genomic alterations in mesenchymal stem cells from 21 myeloma patients (MM-MSCs) and 12 normal donors (ND-MSCs) after in vitro culture expansion. Whereas ND-MSCs were devoid of genomic imbalances, several non-recurrent chromosomal gains and losses (>1 Mb size) were detected in MM-MSCs. Using real-time reverse transcription PCR, we found correlative deregulated expression for five genes encoded in regions for which genomic imbalances were detected using array-CGH. In addition, only MM-MSCs showed a specific pattern of 'hot-spot' regions with discrete (<1 Mb) genomic alterations, some of which were confirmed using fluorescence in situ hybridization (FISH). Within MM-MSC samples, unsupervised cluster analysis did not correlate with particular clinicobiological features of MM patients. We also explored whether cytogenetic abnormalities present in myelomatous plasma cells (PCs) were shared by matching MSCs from the same patients using FISH. All MM-MSCs were cytogenetically normal for the tested genomic alterations. Therefore we cannot support a common progenitor for myeloma PCs and MSCs.
多发性骨髓瘤（MM）的骨髓基质细胞是否存在可能导致该疾病发病机制的基因组改变仍是一个悬而未决的问题。我们进行了基于阵列的比较基因组杂交（array-CGH）分析，以比较21例骨髓瘤患者的间充质干细胞（MM-MSCs）和12例正常供体的间充质干细胞（ND-MSCs）在体外培养扩增后的基因组不平衡改变程度。ND-MSCs没有基因组失衡，而在MM-MSCs中检测到了几种非复发性染色体增减（>1 Mb大小）。使用实时逆转录PCR，我们发现对于在使用array-CGH检测到基因组失衡的区域中编码的五个基因，存在相关的表达失调。此外，只有MM-MSCs显示出具有离散（<1 Mb）基因组改变的“热点”区域的特定模式，其中一些使用荧光原位杂交（FISH）得到了证实。在MM-MSC样本中，无监督聚类分析与MM患者的特定临床生物学特征无关。我们还使用FISH探索了骨髓瘤浆细胞（PCs）中存在的细胞遗传学异常是否与来自同一患者的匹配MSCs共有。对于测试的基因组改变，所有MM-MSCs的细胞遗传学均正常。因此，我们不支持骨髓瘤PCs和MSCs有共同祖细胞的观点。
