Bone marrow mesenchymal stromal cell (MSC) gene profiling in chronic myeloid leukemia (CML) patients at diagnosis and in deep molecular response induced by tyrosine kinase inhibitors (TKIs)
Bone marrow mesenchymal stromal cell (MSC) gene profiling in chronic myeloid leukemia (CML) patients at diagnosis and in deep molecular response induced by tyrosine kinase inhibitors (TKIs)
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DOI：
10.1016/j.leukres.2017.07.007
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发表时间：
2017-09-01
影响因子：
2.7
通讯作者：
Turhan, Ali G.
中科院分区：
文献类型：
--
作者：
Aggoune, Djamel;Sorel, Nathalie;Turhan, Ali G.
虽然它已被充分证明，骨髓间充质干细胞（MSC）从CML患者不属于Ph 1阳性克隆，有越来越多的证据表明，他们可以发挥作用，在白血病的发生过程中或保护白血病干细胞的酪氨酸激酶抑制剂（TKI）的影响。本研究的目的是鉴定诊断时从CML患者分离的MSC（CML-MSC）与来自健康对照的MSC相比差异表达的基因。使用定制的基因分析测定，我们确定了CML-MSC中过表达的六个基因（BMP 1，FOXO 3，MET，MITF，NANOG，PDPN），其中记录了PDPN（PODOPLANIN）和NANOG的两个最高水平。为了确定这种异常特征是否在TKI诱导的深度分子反应中持续存在，我们分析了源自此类患者的MSC（MR-MSC）。该分析表明，尽管存在深度分子反应，但BMP 1、MET、MITF、NANOG和PDPN mRNA在MR-MSC中上调。此外，发现MR-MSC中的BMP 1、MITF和NANOG mRNA表达介于对照MSC和CML-MSC之间。这些结果表明，CML-MSCs表现出异常的基因表达模式，这可能已经建立在白血病的过程中，并坚持在患者的深层分子反应。
Although it has been well-demonstrated that bone marrow mesenchymal stromal cells (MSCs) from CML patients do not belong to the Ph1-positive clone, there is growing evidence that they could play a role in the leukemogenesis process or the protection of leukemic stem cells from the effects of tyrosine kinase inhibitors (TKIs). The aim of the present study was to identify genes differentially expressed in MSCs isolated from CML patients at diagnosis (CML-MSCs) as compared to MSCs from healthy controls. Using a custom gene-profiling assay, we identified six genes over-expressed in CML-MSCs (BMP1, FOXO3, MET, MITF, NANOG, PDPN), with the two highest levels being documented for PDPN (PODOPLANIN) and NANOG. To determine whether this aberrant signature persisted in patients in deep molecular response induced by TKIs, we analyzed MSCs derived from such patients (MR-MSCs). This analysis showed that, despite the deep molecular responses, BMP1, MET, MITF, NANOG, and PDPN mRNA were upregulated in MR-MSCs. Moreover, BMP1, MITF, and NANOG mRNA expressions in MR-MSCs were found to be intermediate between control MSCs and CML-MSCs. These results suggest that CML-MSCs exhibit an abnormal gene expression pattern which might have been established during the leukemogenic process and persist in patients in deep molecular response.