Comprehensive analysis of mesenchymal cells reveals a dysregulated TGF-β/Wnt/HOXB7 axis in patients with myelofibrosis.
Fiche publication
Date publication
octobre 2024
Journal
JCI insight
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GUIDEZ Fabien
Tous les auteurs :
Ganesan S, Awan-Toor S, Guidez F, Maslah N, Rahimy R, Aoun C, Gou P, Guiguen C, Soret J, Ravdan O, Bisio V, Dulphy N, Lobry C, Schlageter MH, Souyri M, Giraudier S, Kiladjian JJ, Chomienne C, Cassinat B
Lien Pubmed
Résumé
Despite the advances in the understanding and treatment of myeloproliferative neoplasm (MPN), the disease remains incurable with the risk of evolution to AML or myelofibrosis (MF). Unfortunately, the evolution of the disease to MF remains still 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 HOXB7 overexpression and more precisely a novel TGFβ-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 reverse the abnormal phenotype of MSCs from myelofibrosis patients, providing the MPN field with a potential novel target to prevent and manage evolution to MF.
Mots clés
Bone marrow, Fibrosis, Hematology
Référence
JCI Insight. 2024 10 29;: