Le suivi in vivo du développement de la polycythémie vera révèle l'anhydrase carbonique 1 comme une cible thérapeutique potentielle
| Autor: | Shohei Murakami, Vilma Barroca, Leïla Perié, Anne Bravard, Jacqueline Bernardino-Sgherri, Amandine Tisserand, Caroline Devanand, Valérie Edmond, Aurélie Magniez, Sabrina Tenreira Bento, Claire Torres, Florence Pasquier, Isabelle Plo, William Vainchenker, Jean-Luc Villeval, Paul-Henri Roméo, Daniel Lewandowski |
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| Přispěvatelé: | CEA- Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris-Saclay, Université Paris Cité (UPCité), Laboratoire Physico-Chimie Curie [Institut Curie] (PCC), Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Cellules souches hématopoïétiques et développement des hémopathies myéloïdes (CSHMyelo), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, INSERM UMR 1287 Département d'hématologie, Dynamique moléculaire de la transformation hématopoïétique (Dynamo), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR) |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Blood Cancer Discov Blood Cancer Discovery Blood Cancer Discovery, 2022, 3 (4), pp.285-297. ⟨10.1158/2643-3230.BCD-21-0039⟩ |
| ISSN: | 2643-3249 2643-3230 |
| DOI: | 10.1158/2643-3230.BCD-21-0039⟩ |
| Popis: | Current murine models of myeloproliferative neoplasms (MPNs) cannot examine how MPNs progress from a single bone marrow source to the entire hematopoietic system. Thus, using transplantation of knock-in JAK2V617F hematopoietic cells into a single irradiated leg, we show development of polycythemia vera (PV) from a single anatomic site in immunocompetent mice. Barcode experiments reveal that grafted JAK2V617F stem/progenitor cells migrate from the irradiated leg to nonirradiated organs such as the contralateral leg and spleen, which is strictly required for development of PV. Mutant cells colonizing the nonirradiated leg efficiently induce PV in nonconditioned recipient mice and contain JAK2V617F hematopoietic stem/progenitor cells that express high levels of carbonic anhydrase 1 (CA1), a peculiar feature also found in CD34+ cells from patients with PV. Finally, genetic and pharmacologic inhibition of CA1 efficiently suppresses PV development and progression in mice and decreases PV patients’ erythroid progenitors, strengthening CA1 as a potent therapeutic target for PV. Significance: Follow-up of hematopoietic malignancies from their initiating anatomic site is crucial for understanding their development and discovering new therapeutic avenues. We developed such an approach, used it to characterize PV progression, and identified CA1 as a promising therapeutic target of PV. This article is highlighted in the In This Issue feature, p. 265 |
| Databáze: | OpenAIRE |
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