Format

Send to

Choose Destination
Leuk Res. 2017 Sep;60:94-102. doi: 10.1016/j.leukres.2017.07.007. Epub 2017 Jul 26.

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).

Author information

1
INSERM, U935, F-86000 Poitiers, France.
2
INSERM, U935, F-86000 Poitiers, France; CHU de Poitiers, Service de Cancérologie Biologique, F-86021 Poitiers, France.
3
CHU de Poitiers, Service d'Anatomie et cytologie pathologiques, F-86021 Poitiers, France; INSERM, U1082, F-86021 Poitiers, France.
4
INSERM, U917, F-35043 Rennes, France.
5
CHU de Tours, Service d'Hématologie Biologique, F-37032 Tours, France; CNRS UMR 7292, équipe LNOx, Université François Rabelais, F-37032 Tours, France.
6
Hôpital Saint Louis, Service d'Hématologie Adulte, F-75000 Paris, France; INSERM, UMRS-1160, IUH-Université Paris Diderot-Paris 7, F-75000 Paris, France.
7
Hôpital l'Archet, Service d'Hématologie Clinique, F-06202 Nice, France.
8
CHU de Caen, Service d'Hématologie, F-14003 Caen, France.
9
Centre Hospitalier de Versailles, Service d'Hématologie et Oncologie, F-78150 Le Chesnay, France; EA4340, Université Versailles-Saint Quentin en Yvelines, Université Paris-Saclay, France.
10
INSERM, CIC-P 0802, F-86000 Poitiers, France; CHU de Poitiers, Service d'Oncologie Hématologique et Thérapie Cellulaire, F-86000, Poitiers, France.
11
CHU Brabois Vandoeuvre, Service d'Hématologie, F-54511 Nancy, France.
12
Hôpital Paul Brousse, Service d'Hématologie Biologique, F-94800 Villejuif, France; NSERM U935, F-94807 Villejuif, France; Université Paris Sud, F-94270 Le Kremlin-Bicêtre, France.
13
INSERM, U935, F-86000 Poitiers, France; Hôpital Paul Brousse, Service d'Hématologie Biologique, F-94800 Villejuif, France; NSERM U935, F-94807 Villejuif, France; Université Paris Sud, F-94270 Le Kremlin-Bicêtre, France; Hôpital Bicêtre, Service d'Hématologie Biologique, F-94270 Le Kremlin Bicêtre, France. Electronic address: turviv33@gmail.com.

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.

KEYWORDS:

Chronic myeloid leukemia; Hematopoietic niche; Mesenchymal stromal cells; TaqMan low-density array

PMID:
28772207
DOI:
10.1016/j.leukres.2017.07.007
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center