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).
Fiche publication
Date publication
juillet 2017
Journal
Leukemia research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GUERCI-BRESLER Agnès
Tous les auteurs :
Aggoune D, Sorel N, Bonnet ML, Goujon JM, Tarte K, Hérault O, Domenech J, Réa D, Legros L, Johnson-Ansa H, Rousselot P, Cayssials E, Guerci-Bresler A, Bennaceur-Griscelli A, Chomel JC, Turhan AG
Lien Pubmed
Résumé
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.
Mots clés
Chronic myeloid leukemia, Hematopoietic niche, Mesenchymal stromal cells, TaqMan low-density array
Référence
Leuk. Res.. 2017 Jul;60:94-102