Carrara R C V, Orellana M D, Fontes A M, Palma P V B, Kashima S, Mendes M R, Coutinho M A, Voltarelli J C, Covas D T
Centro Regional de Hemoterapia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Braz J Med Biol Res. 2007 Jan;40(1):57-67. doi: 10.1590/s0100-879x2007000100008.
Bone marrow is a heterogeneous cell population which includes hematopoietic and mesenchymal progenitor cells. Dysregulated hematopoiesis occurs in chronic myelogenous leukemia (CML), being caused at least in part by abnormalities in the hematopoietic progenitors. However, the role of mesenchymal stem cells (MSCs) in CML has not been well characterized. The objectives of the present study were to observe the biological characteristics of MSCs from CML patients and to determine if MSCs originate in part from donors in CML patients after bone marrow transplantation (BMT). We analyzed MSCs from 5 untreated patients and from 3 CML patients after sex-mismatched allogeneic BMT. Flow cytometry analysis revealed the typical MSC phenotype and in vitro assays showed ability to differentiate into adipocytes and osteoblasts. Moreover, although some RT-PCR data were contradictory, combined fluorescence in situ hybridization analysis showed that MSCs from CML patients do not express the bcr-abl gene. Regarding MSCs of donor origin, although it is possible to detect Y target sequence by nested PCR, the low frequency (0.14 and 0.34%) of XY cells in 2 MSC CML patients by fluorescence in situ hybridization analysis suggests the presence of contaminant hematopoietic cells and the absence of host-derived MSCs in CML patients. Therefore, we conclude that MSCs from CML patients express the typical MSC phenotype, can differentiate into osteogenic and adipogenic lineages and do not express the bcr-abl gene. MSCs cannot be found in recipients 12 to 20 months after BMT. The influence of MSCs on the dysregulation of hematopoiesis in CML patients deserves further investigation.
骨髓是一种异质性细胞群体，其中包括造血祖细胞和间充质祖细胞。慢性粒细胞白血病（CML）中会出现造血失调，这至少部分是由造血祖细胞的异常所导致的。然而，间充质干细胞（MSC）在CML中的作用尚未得到充分阐明。本研究的目的是观察CML患者来源的MSC的生物学特性，并确定在骨髓移植（BMT）后，CML患者的MSC是否部分源自供体。我们分析了5例未经治疗的患者以及3例接受性别不匹配的异基因BMT后的CML患者的MSC。流式细胞术分析揭示了典型的MSC表型，体外试验表明其具有分化为脂肪细胞和成骨细胞的能力。此外，尽管一些逆转录聚合酶链反应（RT-PCR）数据相互矛盾，但联合荧光原位杂交分析表明，CML患者的MSC不表达bcr-abl基因。关于供体来源的MSC，尽管通过巢式PCR有可能检测到Y靶序列，但荧光原位杂交分析显示，2例CML患者的MSC中XY细胞的频率较低（分别为0.14%和0.34%），这表明存在污染的造血细胞，且CML患者中不存在宿主来源的MSC。因此，我们得出结论，CML患者的MSC表达典型的MSC表型，可分化为成骨和成脂谱系，且不表达bcr-abl基因。在BMT后12至20个月的受者中未发现MSC。MSC对CML患者造血失调的影响值得进一步研究。
