| Autor: |
Wu Y; Laboratoire d'Hématologie, CHU de Saint-Etienne, 42055 Saint-Etienne Cedex, France.; UMR 5239, Laboratoire de Biologie et Modélisation de la Cellule, 69364 Lyon, France., Campos L; Laboratoire d'Hématologie, CHU de Saint-Etienne, 42055 Saint-Etienne Cedex, France.; UMR 5239, Laboratoire de Biologie et Modélisation de la Cellule, 69364 Lyon, France., Daguenet E; Département d'Hématologie, Institut de Cancérologie Lucien Neuwirth, 42270 Saint-Priest-en-Jarez Cedex, France., He Z; Biologie, Ingénierie et Imagerie de la Greffe de Cornée (BiiGC), Université Jean Monnet, 42270 Saint-Priest-en-Jarez, France., Picot T; Laboratoire d'Hématologie, CHU de Saint-Etienne, 42055 Saint-Etienne Cedex, France.; UMR 5239, Laboratoire de Biologie et Modélisation de la Cellule, 69364 Lyon, France., Tavernier-Tardy E; UMR 5239, Laboratoire de Biologie et Modélisation de la Cellule, 69364 Lyon, France.; Département d'Hématologie, Institut de Cancérologie Lucien Neuwirth, 42270 Saint-Priest-en-Jarez Cedex, France., Soglu G; Département d'Hématologie, Institut de Cancérologie Lucien Neuwirth, 42270 Saint-Priest-en-Jarez Cedex, France., Guyotat D; UMR 5239, Laboratoire de Biologie et Modélisation de la Cellule, 69364 Lyon, France.; Département d'Hématologie, Institut de Cancérologie Lucien Neuwirth, 42270 Saint-Priest-en-Jarez Cedex, France., Aanei CM; Laboratoire d'Hématologie, CHU de Saint-Etienne, 42055 Saint-Etienne Cedex, France.; UMR 5239, Laboratoire de Biologie et Modélisation de la Cellule, 69364 Lyon, France. |
| Abstrakt: |
Emerging evidence indicates that in myelodysplastic syndromes (MDS), the bone marrow (BM) microenvironment may also contribute to the ineffective, malignant haematopoiesis in addition to the intrinsic abnormalities of haematopoietic stem precursor cells (HSPCs). The BM microenvironment influences malignant haematopoiesis through indirect mechanisms, but the processes by which the BM microenvironment directly contributes to MDS initiation and progression have not yet been elucidated. Our previous data showed that BM-derived stromal cells (BMSCs) from MDS patients have an abnormal expression of focal adhesion kinase (FAK). In this study, we characterise the morpho-phenotypic features and the functional alterations of BMSCs from MDS patients and in FAK knock-downed HS-5 cells. The decreased expression of FAK or its phosphorylated form in BMSCs from low-risk (LR) MDS directly correlates with BMSCs' functional deficiency and is associated with a reduced level of haemoglobin. The downregulation of FAK in HS-5 cells alters their morphology, proliferation, and differentiation capabilities and impairs the expression of several adhesion molecules. In addition, we examine the CD34+ healthy donor (HD)-derived HSPCs' properties when co-cultured with FAK-deficient BMSCs. Both abnormal proliferation and the impaired erythroid differentiation capacity of HD-HSPCs were observed. Together, these results demonstrate that stromal adhesion mechanisms mediated by FAK are crucial for regulating HSPCs' homeostasis. |
