Hélène Gleitz-Broeders: Targeting Stromal Crosstalk to Reverse Bone Marrow Fibrosis
Hélène Gleitz-Broeders, Assistant Professor, Developmental Biology at Erasmus MC, shared an insightful post on LinkedIn:
”Thrilled to share our new publication in HemaSphere Journal!
Our study, “Inhibiting the alarmin‐driven hematopoiesis‐stromal cell crosstalk in primary myelofibrosis ameliorates bone marrow fibrosis”, uncovers how inflammatory signals from malignant hematopoietic cells drive fibrosis— and how targeting them can restore healthier bone marrow function.
Our key findings:
- We show that the S100A8/S100A9 “alarmin” complex produced by the malignant JAK2V617F hematopoietic clone plays a central role in reprogramming stromal cells into fibrosis-driving cells.
- The S100A9 inhibitor tasquinimod not only reduced splenomegaly and fibrosis in preclinical models, but also reversed TGFβ-driven fibrotic reprogramming of megakaryocytes and monocytes.
- Genetic deletion of S100A9 in hematopoietic cells (but not in stroma) improved blood counts, reduced inflammation, and nearly eliminated bone marrow fibrosis.
Why it matters:
- Fibrosis is a major driver of morbidity in myeloproliferative neoplasms, and current treatments have limited ability to reverse it. Our findings point to new strategies—by breaking the inflammatory crosstalk between malignant blood cells and the bone marrow microenvironment—to improve outcomes for patients with primary myelofibrosis.
Huge thanks to our fantastic collaborators:
Stijn Fuchs, Inge Snoeren, Charlotte Boys, James Nagai, Héctor Tejeda Mora, Vanessa Klöker, Jessica Pritchard, Iris Bakker, Marta Gargallo Garasa, Eric Bindels, Julio Saez Rodriguez, Thomas Vogl, Rafael Kramann, MD, PhD, Aurélien Dugourd, Ivan Costa, and Rebekka K. Schneider, MD, PhD
Many thanks to Oncode Institute, ZonMw, Active Biotech AB and European Research Council (ERC) for research support and funding!”
Read the full article here.
Article: Inhibiting the alarmin-driven hematopoiesis-stromal cell crosstalk in primary myelofibrosis ameliorates bone marrow fibrosis
Authors: Hélène F. E. Gleitz, Stijn N. R. Fuchs, Inge A. M. Snoeren, Charlotte Boys, James Nagai, Hector Tejeda-Mora, Vanessa Klöker, Jessica E. Pritchard, Iris J. Bakker, Marta Gargallo Garasa, Eric Bindels, Julio Saez-Rodriguez, Thomas Vogl, Rafael Kramann, Aurélien Dugourd, Ivan G. Costa, Rebekka K. Schneider
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