Authors
Tiffany Phuc Linh Nguyen, Yong Guang Jiang, Betul M Ogan, Andrew D Doyle, Duy T Tran, Jerrold M Ward, Andrew Zhang, Rafaela Ferrer de Oliveira, Francesca Ferraresso, Jacob R Bledsoe, Christian J Kastrup, Matthew J Flick, R Grant Rowe, Thomas H Bugge, Lakmali M Silva
Published in
Blood advances. Jun 18, 2026. Epub Jun 18, 2026.
Abstract
Hematopoietic recovery following myeloablation plays a critical role in the survival of the patients that receive chemotherapy or hematopoietic stem cell transplantation. Understanding the mechanisms underlying hematopoiesis helps identify molecular and/or cellular determinants that could be targeted to enhance hematopoietic recovery. Although several mechanisms by which the plasminogen activation system promotes hematopoietic recovery after myelosuppression have been reported, the specific role fibrinolysis plays in hematopoietic recovery is unclear. The current study employs 5-Fluorouracil-mediated myeloablation in murine models and provides a clear demonstration of uniform extravascular fibrin deposits in the bone marrow niche upon myeloablation. Persistent fibrin deposits in plasminogen-deficient mice lead to failure of hematopoietic recovery. Genetic and pharmacological depletion of fibrinogen following myeloablation restored hematopoietic recovery, revealing the critical role of fibrin in this process. Moreover, defective fibrinolysis led to delayed hematopoietic recovery via a mechanism that involves fibrin engagement with the major myeloid integrin aMb2. Importantly, similar fibrin-rich marrow niches were also observed in human bone marrow injury and failure states. The study identifies a novel molecular pathway that could be therapeutically targeted to enhance hematopoietic recovery following myeloablation.
PMID:
42314039
Bibliographic data and abstract were imported from PubMed on 19 Jun 2026.
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