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Heterogeneity of the bone marrow niche in patients with myeloproliferative neoplasms: ActivinA secretion by mesenchymal stromal cells correlates with the degree of marrow fibrosis
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media Deutschland GmbH, 2020.
-
Abstract
- Mesenchymal stromal cells (MSCs) represent an essential component of the bone marrow (BM) niche and display disease-specific alterations in several myeloid malignancies. The aim of this work was to study possible MSC abnormalities in Philadelphia-negative myeloproliferative neoplasms (MPNs) in relationship to the degree of BM fibrosis. MSCs were isolated from BM of 6 healthy donors (HD) and of 23 MPN patients, classified in 3 groups according to the diagnosis and the grade of BM fibrosis: polycythemia vera and essential thrombocythemia (PV/ET), low fibrosis myelofibrosis (LF-MF), and high fibrosis MF (HF-MF). MSC cultures were established from 21 of 23 MPN patients. MPN-derived MSCs did not exhibit any functional impairment in their adipogenic/osteogenic/chondrogenic differentiation potential and displayed a phenotype similar to HD-derived MSCs but with a decreased expression of CD146. All MPN-MSC lines were negative for the patient-specific hematopoietic clone mutations (JAK2, MPL, CALR). MSCs derived from HF-MF patients displayed a reduced clonogenic potential and a lower growth kinetic compared to MSCs from HD, LF-MF, and PV/ET patients. mRNA levels of hematopoiesis regulatory molecules were unaffected in MSCs from HF-MF compared to HD. Finally, in vitro ActivinA secretion by MSCs was increased in HF-MF compared to LF-MF patients, in association with a lower hemoglobin value. Increased ActivinA immunolabeling on stromal cells and erythroid precursors was also observed in HF-MF BM biopsies. In conclusion, higher grade of BM fibrosis is associated with functional impairment of MSCs and the increased secretion of ActivinA may represent a suitable target for anemia treatment in MF patients.
- Subjects :
- Adult
Male
Myeloid
Stromal cell
Myeloproliferative neoplasm
myelofibrosis
myeloproliferative neoplasms
Cohort Studies
03 medical and health sciences
ActivinA
0302 clinical medicine
Polycythemia vera
Fibrosis
Bone Marrow
medicine
Humans
Myelofibrosis
mesenchymal stromal cells
Polycythemia Vera
Cells, Cultured
Aged
Myeloproliferative Disorders
Essential thrombocythemia
business.industry
Mesenchymal stromal cell
Mesenchymal stem cell
Myelofibrosi
Cell Differentiation
Mesenchymal Stem Cells
Hematology
General Medicine
Middle Aged
medicine.disease
Activins
medicine.anatomical_structure
Primary Myelofibrosis
030220 oncology & carcinogenesis
Cancer research
Female
Bone marrow
business
030215 immunology
Thrombocythemia, Essential
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....d9e22b24692a4857d74685378843e33b