Jootar Saengsuree, Pornprasertsud Nida, Petvises Sawang, Rerkamnuaychoke Busaba, Disthabanchong Sinee, Pakakasama Samart, Ungkanont Artit, Hongeng Suradej
Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Leuk Res. 2006 Dec;30(12):1493-8. doi: 10.1016/j.leukres.2006.04.013. Epub 2006 Jul 12.
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of hematopoietic stem cells. It is characterized at cytogenetic level by the Philadelphia (Ph) chromosome and at the molecular level by the BCR/ABL gene rearrangement. Bone marrow derived mesenchymal stem cells (MSCs) are also pluripotent stem cells that can differentiate into several mesenchymal tissues. To date, no study has been performed to characterize whether MSCs from CML harbor the abnormal Ph chromosome similar to CML bone marrow cells. We isolated and characterized MSCs from diagnostic marrow samples (n=11) and showed that MSCs can be readily isolated from CML marrow and exhibit major expansion potential as well as intact osteogenic differentiation ability. Moreover, they do not harbor the Ph chromosome confirmed by fluorescence in situ hybridization (FISH) and reverse transcriptase polymerase chain reaction (RT-PCR). Thus, we demonstrated that CML marrow is an abundant source of MSCs appearing through both FISH and RT-PCR not to be involved by the malignant process of CML. Furthermore, these MSCs from a CML patient could support in vitro cord blood expansion as those MSCs from a normal donor. Since MSCs are able to support engraftment of hematopoietic stem cells in stem cell transplantation (SCT) as well as suppress alloreactive T cells causing graft-versus-host disease, this current report thus provides evidence that in a SCT setting of CML patients, autologous MSCs could be a source of stem cell support in future cell therapy applications.
慢性髓性白血病(CML)是一种造血干细胞的克隆性骨髓增殖性疾病。其在细胞遗传学水平上以费城(Ph)染色体为特征,在分子水平上以BCR/ABL基因重排为特征。骨髓来源的间充质干细胞(MSCs)也是多能干细胞,可分化为多种间充质组织。迄今为止,尚未进行研究来表征CML患者的MSCs是否携带有与CML骨髓细胞相似的异常Ph染色体。我们从诊断性骨髓样本(n = 11)中分离并鉴定了MSCs,结果表明MSCs能够很容易地从CML骨髓中分离出来,具有主要的扩增潜力以及完整的成骨分化能力。此外,通过荧光原位杂交(FISH)和逆转录聚合酶链反应(RT-PCR)证实它们不携带Ph染色体。因此,我们证明CML骨髓是MSCs的丰富来源,通过FISH和RT-PCR均显示其未被CML的恶性过程累及。此外,来自CML患者的这些MSCs能够像来自正常供体的MSCs一样支持体外脐血扩增。由于MSCs能够在干细胞移植(SCT)中支持造血干细胞的植入,并抑制引起移植物抗宿主病的同种反应性T细胞,因此本报告提供了证据,表明在CML患者的SCT环境中,自体MSCs在未来的细胞治疗应用中可能是干细胞支持的一个来源。