Abstract
Splenic hematopoiesis is a major feature in the course of myelofibrosis (MF). In fact, the spleen of patients with MF contains malignant hematopoietic stem cells retaining a complete differentiation program, suggesting both a pivotal role of the spleen in maintaining the disease and a tight regulation of hematopoiesis by the splenic microenvironment, in particular by mesenchymal stromal cells (MSCs). Little is known about splenic MSCs (Sp-MSCs), both in normal and in pathological context. In this work, we have in vitro expanded and characterized Sp-MSCs from 25 patients with MF and 13 healthy subjects (HS). They shared similar phenotype, growth kinetics, and differentiation capacity. However, MF Sp-MSCs expressed significant lower levels of nestin, and favored megakaryocyte (Mk) differentiation in vitro at a larger extent than their normal counterpart. Moreover, they showed a significant upregulation of matrix metalloprotease 2 (MMP2) and fibronectin 1 (FN1) genes both at mRNA expression and at protein level, and, finally, developed genetic abnormalities which were never detected in HS-derived Sp-MSCs. Our data point toward the existence of a defective splenic niche in patients with MF that could be responsible of some pathological features of the disease, including the increased trafficking of CD34+ cells and the expansion of the megakaryocytic lineage.
| Original language | English |
|---|---|
| Pages (from-to) | 615-622 |
| Number of pages | 8 |
| Journal | American Journal of Hematology |
| Volume | 93 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2018 |
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The spleen of patients with myelofibrosis harbors defective mesenchymal stromal cells. / AGIMM Investigators.
In: American Journal of Hematology, Vol. 93, No. 5, 05.2018, p. 615-622.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The spleen of patients with myelofibrosis harbors defective mesenchymal stromal cells
AU - AGIMM Investigators
AU - Avanzini, Maria Antonietta
AU - Abbonante, Vittorio
AU - Catarsi, Paolo
AU - Dambruoso, Irene
AU - Mantelli, Melissa
AU - Poletto, Valentina
AU - Lenta, Elisa
AU - Guglielmelli, Paola
AU - Croce, Stefania
AU - Cobianchi, Lorenzo
AU - Jemos, Basilio
AU - Campanelli, Rita
AU - Bonetti, Elisa
AU - Di Buduo, Christian Andrea
AU - Salmoiraghi, Silvia
AU - Villani, Laura
AU - Massa, Margherita
AU - Boni, Marina
AU - Zappatore, Rita
AU - Iurlo, Alessandra
AU - Rambaldi, Alessandro
AU - Vannucchi, Alessandro Maria
AU - Bernasconi, Paolo
AU - Balduini, Alessandra
AU - Barosi, Giovanni
AU - Rosti, Vittorio
N1 - © 2018 Wiley Periodicals, Inc.
PY - 2018/5
Y1 - 2018/5
N2 - Splenic hematopoiesis is a major feature in the course of myelofibrosis (MF). In fact, the spleen of patients with MF contains malignant hematopoietic stem cells retaining a complete differentiation program, suggesting both a pivotal role of the spleen in maintaining the disease and a tight regulation of hematopoiesis by the splenic microenvironment, in particular by mesenchymal stromal cells (MSCs). Little is known about splenic MSCs (Sp-MSCs), both in normal and in pathological context. In this work, we have in vitro expanded and characterized Sp-MSCs from 25 patients with MF and 13 healthy subjects (HS). They shared similar phenotype, growth kinetics, and differentiation capacity. However, MF Sp-MSCs expressed significant lower levels of nestin, and favored megakaryocyte (Mk) differentiation in vitro at a larger extent than their normal counterpart. Moreover, they showed a significant upregulation of matrix metalloprotease 2 (MMP2) and fibronectin 1 (FN1) genes both at mRNA expression and at protein level, and, finally, developed genetic abnormalities which were never detected in HS-derived Sp-MSCs. Our data point toward the existence of a defective splenic niche in patients with MF that could be responsible of some pathological features of the disease, including the increased trafficking of CD34+ cells and the expansion of the megakaryocytic lineage.
AB - Splenic hematopoiesis is a major feature in the course of myelofibrosis (MF). In fact, the spleen of patients with MF contains malignant hematopoietic stem cells retaining a complete differentiation program, suggesting both a pivotal role of the spleen in maintaining the disease and a tight regulation of hematopoiesis by the splenic microenvironment, in particular by mesenchymal stromal cells (MSCs). Little is known about splenic MSCs (Sp-MSCs), both in normal and in pathological context. In this work, we have in vitro expanded and characterized Sp-MSCs from 25 patients with MF and 13 healthy subjects (HS). They shared similar phenotype, growth kinetics, and differentiation capacity. However, MF Sp-MSCs expressed significant lower levels of nestin, and favored megakaryocyte (Mk) differentiation in vitro at a larger extent than their normal counterpart. Moreover, they showed a significant upregulation of matrix metalloprotease 2 (MMP2) and fibronectin 1 (FN1) genes both at mRNA expression and at protein level, and, finally, developed genetic abnormalities which were never detected in HS-derived Sp-MSCs. Our data point toward the existence of a defective splenic niche in patients with MF that could be responsible of some pathological features of the disease, including the increased trafficking of CD34+ cells and the expansion of the megakaryocytic lineage.
U2 - 10.1002/ajh.25047
DO - 10.1002/ajh.25047
M3 - Article
C2 - 29359451
VL - 93
SP - 615
EP - 622
JO - American Journal of Hematology
JF - American Journal of Hematology
SN - 0361-8609
IS - 5
ER -