Increased CXCL4 expression in hematopoietic cells links inflammation and progression of bone marrow fibrosis in MPN.
Blood
; 136(18): 2051-2064, 2020 10 29.
Article
en En
| MEDLINE
| ID: mdl-32726410
ABSTRACT
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) that leads to progressive bone marrow (BM) fibrosis. Although the cellular mutations involved in the pathogenesis of PMF have been extensively investigated, the sequential events that drive stromal activation and fibrosis by hematopoietic-stromal cross-talk remain elusive. Using an unbiased approach and validation in patients with MPN, we determined that the differential spatial expression of the chemokine CXCL4/platelet factor-4 marks the progression of fibrosis. We show that the absence of hematopoietic CXCL4 ameliorates the MPN phenotype, reduces stromal cell activation and BM fibrosis, and decreases the activation of profibrotic pathways in megakaryocytes, inflammation in fibrosis-driving cells, and JAK/STAT activation in both megakaryocytes and stromal cells in 3 murine PMF models. Our data indicate that higher CXCL4 expression in MPN has profibrotic effects and is a mediator of the characteristic inflammation. Therefore, targeting CXCL4 might be a promising strategy to reduce inflammation in PMF.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Médula Ósea
/
Fibrosis
/
Factor Plaquetario 4
/
Mielofibrosis Primaria
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Inflamación
/
Trastornos Mieloproliferativos
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Blood
Año:
2020
Tipo del documento:
Article
País de afiliación:
Países Bajos