CXCL8 secreted by immature granulocytes inhibits WT hematopoiesis in chronic myelomonocytic leukemia.

Autor: Deschamps P; INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France., Wacheux M; INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France., Gosseye A; INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France., Morabito M; INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France., Pagès A; INSERM U1018, Gustave Roussy Cancer Center, Villejuif, France., Lyne AM; Institut Curie, PSL Research University, Paris, France.; INSERM, U900, Paris, France.; MINES ParisTech, CBIO-Centre for Computational Biology, PSL Research University, Paris, France., Alfaro A; INSERM US23, CNRS UAR 3655, Gustave Roussy Cancer Center, Villejuif, France., Rameau P; INSERM US23, CNRS UAR 3655, Gustave Roussy Cancer Center, Villejuif, France., Imanci A; INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France., Chelbi R; INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France.; INOVARION, Paris, France., Marchand V; INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France., Renneville A; INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France.; Department of Medical Biology and Pathology, Gustave Roussy, Villejuif, France., Patnaik MM; Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA., Lapierre V; Cellular Therapy Department, Gustave Roussy Cancer Center, Villejuif, France., Badaoui B; Department of Hematology and Immunology, Henri-Mondor Hospital, AP-HP, Créteil, France.; University of Paris Est Créteil, INSERM, IMRB, Créteil, France., Wagner-Ballon O; Department of Hematology and Immunology, Henri-Mondor Hospital, AP-HP, Créteil, France.; University of Paris Est Créteil, INSERM, IMRB, Créteil, France., Berthon C; Clinical Hematology Department, University Hospital, Lille, France., Braun T; Clinical Hematology Department, Hôpital Avicenne, Bobigny, France., Willekens C; INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.; Hematology Department, Gustave Roussy Cancer Center, Villejuif, France., Itzykson R; Adult Hematology Department, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.; Université Paris Cité, Génomes, Biologie Cellulaire et Thérapeutique U944, INSERM, CNRS, Paris, France., Fenaux P; Adult Hematology Department, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.; Université Paris Cité, Génomes, Biologie Cellulaire et Thérapeutique U944, INSERM, CNRS, Paris, France., Thépot S; Clinical Hematology Department, University Hospital, Angers, France., Etienne G; Clinical Hematology Department, Institut Bergonié, Bordeaux, France., Elvira-Matelot E; INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France., Porteu F; INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France., Droin N; INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France.; INSERM US23, CNRS UAR 3655, Gustave Roussy Cancer Center, Villejuif, France., Perié L; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR168, Laboratoire Physico-Chimie Curie, Paris, France., Laplane L; INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France.; Institut d'Histoire et Philosophie des Sciences et des Techniques, CNRS U8590, Université Paris I Panthéon-Sorbonne, Paris, France., Solary E; INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France.; Hematology Department, Gustave Roussy Cancer Center, Villejuif, France., Selimoglu-Buet D; INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France.
Jazyk: angličtina
Zdroj: The Journal of clinical investigation [J Clin Invest] 2024 Sep 17; Vol. 134 (22). Date of Electronic Publication: 2024 Sep 17.
DOI: 10.1172/JCI180738
Abstrakt: Chronic myelomonocytic leukemia (CMML) is a severe myeloid malignancy with limited therapeutic options. Single-cell analysis of clonal architecture demonstrates early clonal dominance with few residual WT hematopoietic stem cells. Circulating myeloid cells of the leukemic clone and the cytokines they produce generate a deleterious inflammatory climate. Our hypothesis is that therapeutic control of the inflammatory component in CMML could contribute to stepping down disease progression. The present study explored the contribution of immature granulocytes (iGRANs) to CMML progression. iGRANs were detected and quantified in the peripheral blood of patients by spectral and conventional flow cytometry. Their accumulation was a potent and independent poor prognostic factor. These cells belong to the leukemic clone and behaved as myeloid-derived suppressor cells. Bulk and single-cell RNA-Seq revealed a proinflammatory status of iGRAN that secreted multiple cytokines of which CXCL8 was at the highest level. This cytokine inhibited the proliferation of WT but not CMML hematopoietic stem and progenitor cells (HSPCs) in which CXCL8 receptors were downregulated. CXCL8 receptor inhibitors and CXCL8 blockade restored WT HSPC proliferation, suggesting that relieving CXCL8 selective pressure on WT HSPCs is a potential strategy to slow CMML progression and restore some healthy hematopoiesis.
Databáze: MEDLINE
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