AML patient blasts exhibit polarization defects upon interaction with bone marrow stromal cells
Year: 2025
Type: article
Abstract: Hematopoietic stem and progenitor cells (HSPCs) polarize in contact with the bone marrow stromal cells constituting their niche. Given the role of cell polarity in protection against tumorigenesis and the importance of the niche in the progression of acute myeloid leukemias (AMLs), we investigated the polarization capacities of leukemic blasts. Using engineered micro-niches and centrosome position with respect to the contact site with stromal cells as a proxy for cell polarization, we show that AML cell lines and primary cells from AML patient blasts are unable to polarize in contact with healthy stromal cells. Exposure to AML patient-derived stromal cells compromises the polarization of healthy adult HSPCs and AML blasts from patients. When cultured in “bone-marrow-on-a-chip”, stromal cells from a leukemic niche stimulate the migration of healthy HSPCs and AML blast. These results reveal the detrimental influences of both intrinsic transformation and extrinsic contact with transformed stromal cells on the polarization of AML blasts.
Source: EMBO Reports
Authors: Khansa Saadallah, Benoît Vianay, Louise Bonnemay, Hélène Pasquer, Lois Kelly, Stéphanie Mathis, Cécile Culeux, Raphael Marie, Paul Arthur Meslin, Sofiane Fodil, Paul Chaintreuil, Emeline Kerreneur, Arnaud Jacquel, Emmanuel Raffoux, Rémy Nizard, Camille Lobry, Laurent Blanchoin, Lina Benajiba, Manuel Théry
Institutions: Université Paris Cité, Institut Pierre-Gilles de Gennes pour la Microfluidique, Hôpital Saint-Louis, HIPI - Immunologie humaine, physiopathologie et immunithérapie, Chimie Biologie Innovation, Institut de recherche Saint-Louis, ESPCI Paris, Centre National de la Recherche Scientifique, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, CEA Grenoble, Laboratoire Physiologie Cellulaire & Végétale, Université Grenoble Alpes, Inserm, Génomes, biologie cellulaire et thérapeutiques, Assistance Publique – Hôpitaux de Paris, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire, Hôpital Lariboisière
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $7,990
OpenAlex ID: W4411216860