Related Experiment Video
Updated: Jun 9, 2025
Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
Comprehensive analysis of mesenchymal cells reveals a dysregulated TGF-β/WNT/HOXB7 axis in patients with
Saravanan Ganesan1, Sarah Awan-Toor1, Fabien Guidez1,2
1INSERM UMRS 1131, Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France.
Abstract:
Despite the advances in the understanding and treatment of myeloproliferative neoplasm (MPN), the disease remains incurable with the risk of evolution to acute myeloid leukemia or myelofibrosis (MF). Unfortunately, the evolution of the disease to MF remains poorly understood, impeding preventive and therapeutic options. Recent studies in solid tumor microenvironment and organ fibrosis have shed instrumental insights on their respective pathogenesis and drug resistance, yet such precise data are lacking in MPN. In this study, through a patient sample-driven transcriptomic and epigenetic description of the MF microenvironment landscape and cell-based analyses, we identify homeobox B7 (HOXB7) overexpression and more precisely a potentially novel TGF-β/WNT/HOXB7 pathway as associated to a pro-fibrotic and pro-osteoblastic biased differentiation of mesenchymal stromal cells (MSCs). Using gene-based and chemical inhibition of this pathway, we reversed the abnormal phenotype of MSCs from patients with MF, providing the MPN field a potentially novel target to prevent and manage evolution to MF.
Insights
Researchers identified a novel TGF-β/WNT/HOXB7 pathway driving myelofibrosis (MF) in myeloproliferative neoplasms (MPN). Inhibiting this pathway reversed abnormal cell behavior, offering a new therapeutic target for MPN-MF progression.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Myeloproliferative neoplasms (MPN) are incurable, with a significant risk of progressing to acute myeloid leukemia or myelofibrosis (MF).
- The pathogenesis of MPN evolution to MF is poorly understood, hindering the development of targeted therapies.
- Insights from solid tumor and fibrosis research highlight the importance of the microenvironment, but specific data for MPN-MF is lacking.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying the evolution of MPN to MF.
- To identify novel therapeutic targets for preventing or managing MPN progression to MF.
Main Methods:
- Transcriptomic and epigenetic analysis of MF microenvironment in patient samples.
- Cell-based assays to investigate the role of identified pathways.
- Inhibition studies using gene-based and chemical approaches targeting the novel pathway.
Main Results:
- Identified homeobox B7 (HOXB7) overexpression in the MF microenvironment.
- Discovered a novel pro-fibrotic and pro-osteoblastic signaling pathway involving TGF-β/WNT/HOXB7.
- Demonstrated that inhibition of this pathway reversed the abnormal differentiation of mesenchymal stromal cells (MSCs) from MF patients.
Conclusions:
- The TGF-β/WNT/HOXB7 pathway is implicated in the pathogenesis of MF in MPN.
- Targeting this pathway offers a promising strategy to prevent or treat MPN evolution to MF.
- HOXB7 and its associated pathway represent a potential novel therapeutic target for MPN.
More Related Videos
06:54Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
06:02Development of an In Vitro Assay to Evaluate Contractile Function of Mesenchymal Cells that Underwent Epithelial-Mesenchymal Transition
Published on: June 10, 2016
