Osteogenic Potential of Mesenchymal Stromal Cells Contributes to Primary Myelofibrosis. - Archive ouverte HAL Access content directly
Journal Articles Cancer Research Year : 2015

Osteogenic Potential of Mesenchymal Stromal Cells Contributes to Primary Myelofibrosis.

(1, 2, 3, 4) , (1, 2) , (5) , (6) , (1, 2) , (7, 8) , (8) , (1, 2) , (1, 2) , (9) , (10) , (10) , (11) , (3) , (5) , (12) , (13) , (14) , (6) , (15, 1) , (1, 2, 4)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Lisa Pieri
  • Function : Author
Sandrine Schmutz
  • Function : Author
Patricia Albanese
  • Function : Author
Emilie Henault
  • Function : Author
Olivier Pierre-Louis
Alessandro M Vannucchi
  • Function : Author

Abstract

Primary myelofibrosis is a myeloproliferative neoplasm that is a precursor to myeloid leukemia. Dysmegakaryopoiesis and extramedullary hematopoiesis characterize primary myelofibrosis, which is also associated with bone marrow stromal alterations marked by fibrosis, neoangiogenesis, and osteomyelosclerosis. In particular, contributions to primary myelofibrosis from mesenchymal stromal cells (MSC) have been suggested by mouse studies, but evidence in humans remains lacking. In this study, we show that bone marrow MSCs from primary myelofibrosis patients exhibit unique molecular and functional abnormalities distinct from other myeloproliferative neoplasms and these abnormalities are maintained stably ex vivo in the absence of leukemic cells. Primary myelofibrosis-MSC overexpressed heparin-binding cytokines, including proinflammatory TGFβ1 and osteogenic BMP-2, as well as glycosaminoglycans such as heparan sulfate and chondroitin sulfate. Transcriptome and functional analyses revealed alterations in MSC differentiation characterized by an increased osteogenic potential and a TGFβ1 signaling signature. Accordingly, phospho-Smad2 levels were intrinsically increased in primary myelofibrosis-MSC along with enhanced expression of the master bone regulator RUNX2, while inhibition of the endogenous TGFβ1 receptor TGFβR1 impaired osteogenic differentiation in these MSCs. Taken together, our results define the source of a critical osteogenic function in primary myelofibrosis that supports its pathophysiology, suggesting that combined targeting of both the hematopoietic and stromal cell compartments in primary myelofibrosis patients may heighten therapeutic efficacy. Cancer Res; 75(22); 4753-65. ©2015 AACR.
Not file

Dates and versions

pasteur-01234951 , version 1 (27-11-2015)

Identifiers

Cite

Christophe Martinaud, Christophe Desterke, Johanna Konopacki, Lisa Pieri, Frédéric Torossian, et al.. Osteogenic Potential of Mesenchymal Stromal Cells Contributes to Primary Myelofibrosis.. Cancer Research, 2015, 75 (22), pp.4753-65. ⟨10.1158/0008-5472.CAN-14-3696⟩. ⟨pasteur-01234951⟩
215 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More