Wöhrer S, Rabitsch W, Shehata M, Kondo R, Esterbauer H, Streubel B, Sillaber C, Raderer M, Jaeger U, Zielinski C, Valent P
Department of Internal Medicine 1, Division of Bone Marrow Transplantation, Medical University of Vienna, Vienna, Austria.
Anticancer Res. 2007 Nov-Dec;27(6B):3837-41.
Human mesenchymal stem cells (MSCs) are thought to be multipotent cells which primarily reside in the bone marrow. Besides their well-known ability to replicate as undifferentiated cells and to differentiate into diverse lineages of mesenchymal tissues, they were recently suggested to also give rise to haematopoietic and leukaemic/cancer stem cells. In this study, the relationship between MSCs and leukemic stem cells in patients with either chronic myelogenous leukaemia (CML) or the more primitive variant, Ph+ bi-phenotypic leukaemia was investigated.
Cultured MSCs from 5 patients with CML and 3 patients with bi-phenotypic Ph+ leukaemia, all of them positive for BCP-ABL, were analysed with conventional cytogenetics, fluorescence in situ hybridisation (FISH) and polymerase chain reaction (PCR) for the presence of t(9;22) and BCR-ABL. MSCs were characterised phenotypically with surface markers (+CD73, +CD90, +CD105, -CD34, -CD45) and functionally through their potential to differentiate into both adipocytes and osteoblasts.
MSCs could be cultivated from seven patients. These cells were BCR-ABL negative when analysed with conventional cytogenetics and FISH. Further cytogenetic analysis revealed a normal set of chromosomes without any aberrations. Two patients were BCR-ABL-positive when analysed with PCR, probably as a result of MSC contamination with macrophages.
MSCs in patients with CML or Ph+ bi-phenotypic leukaemia are not related to the malignant cell clone.
人间充质干细胞（MSCs）被认为是多能细胞，主要存在于骨髓中。除了其众所周知的作为未分化细胞进行复制并分化为多种间充质组织谱系的能力外，最近还表明它们也可产生造血干细胞和白血病/癌症干细胞。在本研究中，调查了慢性粒细胞白血病（CML）患者或更原始的变异型Ph+双表型白血病患者中MSCs与白血病干细胞之间的关系。
对5例CML患者和3例双表型Ph+白血病患者培养的MSCs进行分析，所有患者均为BCR-ABL阳性，采用常规细胞遗传学、荧光原位杂交（FISH）和聚合酶链反应（PCR）检测t(9;22)和BCR-ABL的存在情况。通过表面标志物（+CD73、+CD90、+CD105、-CD34、-CD45）对MSCs进行表型鉴定，并通过其分化为脂肪细胞和成骨细胞的潜能进行功能鉴定。
从7例患者中培养出了MSCs。用常规细胞遗传学和FISH分析时，这些细胞BCR-ABL阴性。进一步的细胞遗传学分析显示染色体组正常，无任何畸变。2例患者用PCR分析时BCR-ABL阳性，可能是由于MSCs被巨噬细胞污染所致。
CML或Ph+双表型白血病患者的MSCs与恶性细胞克隆无关。
