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). Aggoune, D., Sorel, N., Bonnet, M., Goujon, J., Tarte, K., Hérault, O., Domenech, J., Réa, D., Legros, L., Johnson-Ansa, H., Rousselot, P., Cayssials, E., Guerci-Bresler, A., Bennaceur-Griscelli, A., Chomel, J., & Turhan, A. G. Leukemia Research, 60:94–102, July, 2017.
doi  abstract   bibtex   
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.
@article{aggoune_bone_2017,
	title = {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})},
	volume = {60},
	issn = {1873-5835},
	doi = {10.1016/j.leukres.2017.07.007},
	abstract = {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.},
	language = {eng},
	journal = {Leukemia Research},
	author = {Aggoune, Djamel and Sorel, Nathalie and Bonnet, Marie-Laure and Goujon, Jean-Michel and Tarte, Karin and Hérault, Olivier and Domenech, Jorge and Réa, Delphine and Legros, Laurence and Johnson-Ansa, Hyacinthe and Rousselot, Philippe and Cayssials, Emilie and Guerci-Bresler, Agnès and Bennaceur-Griscelli, Annelise and Chomel, Jean-Claude and Turhan, Ali G.},
	month = jul,
	year = {2017},
	pmid = {28772207},
	keywords = {Chronic myeloid leukemia, Hematopoietic niche, Mesenchymal Stromal Cells, TaqMan low-density array},
	pages = {94--102},
}

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