Your browser doesn't support javascript.
loading
Heterogeneous bone-marrow stromal progenitors drive myelofibrosis via a druggable alarmin axis.
Leimkühler, Nils B; Gleitz, Hélène F E; Ronghui, Li; Snoeren, Inge A M; Fuchs, Stijn N R; Nagai, James S; Banjanin, Bella; Lam, King H; Vogl, Thomas; Kuppe, Christoph; Stalmann, Ursula S A; Büsche, Guntram; Kreipe, Hans; Gütgemann, Ines; Krebs, Philippe; Banz, Yara; Boor, Peter; Tai, Evelyn Wing-Yin; Brümmendorf, Tim H; Koschmieder, Steffen; Crysandt, Martina; Bindels, Eric; Kramann, Rafael; Costa, Ivan G; Schneider, Rebekka K.
Afiliación
  • Leimkühler NB; Department of Hematology, Erasmus Medical Center, Rotterdam 3015GD, the Netherlands.
  • Gleitz HFE; Department of Hematology, Erasmus Medical Center, Rotterdam 3015GD, the Netherlands.
  • Ronghui L; Institute for Computational Genomics, Faculty of Medicine, RWTH Aachen University, Aachen 52074 Germany.
  • Snoeren IAM; Department of Hematology, Erasmus Medical Center, Rotterdam 3015GD, the Netherlands.
  • Fuchs SNR; Department of Hematology, Erasmus Medical Center, Rotterdam 3015GD, the Netherlands.
  • Nagai JS; Institute for Computational Genomics, Faculty of Medicine, RWTH Aachen University, Aachen 52074 Germany.
  • Banjanin B; Department of Hematology, Erasmus Medical Center, Rotterdam 3015GD, the Netherlands.
  • Lam KH; Department of Pathology, Erasmus Medical Center, Rotterdam 3015GD, the Netherlands.
  • Vogl T; Institute of Immunology, University of Münster, Münster 49148, Germany.
  • Kuppe C; Division of Nephrology and Clinical Immunology, Faculty of Medicine, RWTH Aachen University, Aachen 52074, Germany.
  • Stalmann USA; Department of Hematology, Erasmus Medical Center, Rotterdam 3015GD, the Netherlands.
  • Büsche G; Institute of Pathology, Hannover Medical School, Hannover 30625, Germany.
  • Kreipe H; Institute of Pathology, Hannover Medical School, Hannover 30625, Germany.
  • Gütgemann I; Institute of Pathology, University of Bonn, Bonn 53127, Germany.
  • Krebs P; Institute of Pathology, University of Bern, Bern 3012, Switzerland.
  • Banz Y; Institute of Pathology, University of Bern, Bern 3012, Switzerland.
  • Boor P; Institute of Pathology, Faculty of Medicine, RWTH Aachen University, Aachen 52074, Germany.
  • Tai EW; Institute of Pathology, Faculty of Medicine, RWTH Aachen University, Aachen 52074, Germany.
  • Brümmendorf TH; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen 52074, Germany.
  • Koschmieder S; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen 52074, Germany.
  • Crysandt M; Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen 52074, Germany.
  • Bindels E; Department of Hematology, Erasmus Medical Center, Rotterdam 3015GD, the Netherlands.
  • Kramann R; Division of Nephrology and Clinical Immunology, Faculty of Medicine, RWTH Aachen University, Aachen 52074, Germany; Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, Aachen 52074, Germany.
  • Costa IG; Institute for Computational Genomics, Faculty of Medicine, RWTH Aachen University, Aachen 52074 Germany.
  • Schneider RK; Department of Hematology, Erasmus Medical Center, Rotterdam 3015GD, the Netherlands; Department of Cell Biology, Institute for Biomedical Engineering, Faculty of Medicine, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany; Oncode Institute, Erasmus Medical Center, Rotterdam 3015GD, th
Cell Stem Cell ; 28(4): 637-652.e8, 2021 04 01.
Article en En | MEDLINE | ID: mdl-33301706
Functional contributions of individual cellular components of the bone-marrow microenvironment to myelofibrosis (MF) in patients with myeloproliferative neoplasms (MPNs) are incompletely understood. We aimed to generate a comprehensive map of the stroma in MPNs/MFs on a single-cell level in murine models and patient samples. Our analysis revealed two distinct mesenchymal stromal cell (MSC) subsets as pro-fibrotic cells. MSCs were functionally reprogrammed in a stage-dependent manner with loss of their progenitor status and initiation of differentiation in the pre-fibrotic and acquisition of a pro-fibrotic and inflammatory phenotype in the fibrotic stage. The expression of the alarmin complex S100A8/S100A9 in MSC marked disease progression toward the fibrotic phase in murine models and in patient stroma and plasma. Tasquinimod, a small-molecule inhibiting S100A8/S100A9 signaling, significantly ameliorated the MPN phenotype and fibrosis in JAK2V617F-mutated murine models, highlighting that S100A8/S100A9 is an attractive therapeutic target in MPNs.
Asunto(s)
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Mielofibrosis Primaria / Células Madre Mesenquimatosas / Trastornos Mieloproliferativos Límite: Animals / Humans Idioma: En Revista: Cell Stem Cell Año: 2021 Tipo del documento: Article País de afiliación: Países Bajos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Mielofibrosis Primaria / Células Madre Mesenquimatosas / Trastornos Mieloproliferativos Límite: Animals / Humans Idioma: En Revista: Cell Stem Cell Año: 2021 Tipo del documento: Article País de afiliación: Países Bajos