ANKRD26 is a new regulator of type I cytokine receptor signaling in normal and pathological hematopoiesis.

Autor:	Basso-Valentina F; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer; Ecole Doctorale Hematopoïèse, Oncogénèse et Biothérapie, Université Paris Diderot, Université Sorbonne Paris Cité, Paris., Donada A; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer; Ecole Doctorale Hematopoïèse, Oncogénèse et Biothérapie, Université Paris Diderot, Université Sorbonne Paris Cité, Paris., Manchev VT; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer., Lisetto M; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer., Balayn N; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer., Martin JE; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer; Ecole Doctorale Hematopoïèse, Oncogénèse et Biothérapie, Université Paris Diderot, Université Sorbonne Paris Cité, Paris., Muller D; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer., Oyarzun CPM; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer., Duparc H; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer., Arkoun B; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer., Cumin A; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer; Dipartimento di scienze della vita, University of Trieste, Italy; University of Paris Diderot, Paris., Faivre L; Assistance Publique-Hôpitaux de Paris, Hôpital St Louis, Unité Thérapie Cellulaire., Droin N; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer., Biunno I; Integrated Systems Engineering, Bresso-Milano, Italy; Institute for Genetic and Biomedical Research-CNR, Milano., Pecci A; Department of Internal Medicine, University of Pavia, Pavia, Italy; General Medicine 1, IRCCS Policlinico San Matteo Foundation, Pavia., Balduini A; Department of Molecular Medicine, University of Pavia, Pavia, Italy; Department of Biomedical Engineering, Tufts University, Medford., Debili N; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer., Antony-Debré I; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer., Marty C; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer., Vainchenker W; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer., Plo I; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer., Favier R; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer; Assistance Publique-Hôpitaux de Paris, Hôpital Armand Trousseau, Centre de Référence des pathologies plaquettaires, Paris., Raslova H; INSERM, UMR 1287, Gustave Roussy, Université Paris Saclay, Villejuif France, Equipe labellisée Ligue Nationale contre le Cancer. hana.raslova@gustaveroussy.fr.
Jazyk:	angličtina
Zdroj:	Haematologica [Haematologica] 2023 Aug 01; Vol. 108 (8), pp. 2130-2145. Date of Electronic Publication: 2023 Aug 01.
DOI:	10.3324/haematol.2022.282049
Abstrakt:	Sustained ANKRD26 expression associated with germline ANKRD26 mutations causes thrombocytopenia 2 (THC2), an inherited platelet disorder associated with a predisposition to leukemia. Some patients also present with erythrocytosis and/or leukocytosis. Using multiple human-relevant in vitro models (cell lines, primary patients' cells and patient-derived induced pluripotent stem cells) we demonstrate for the first time that ANKRD26 is expressed during the early steps of erythroid, megakaryocyte and granulocyte differentiation, and is necessary for progenitor cell proliferation. As differentiation progresses, ANKRD26 expression is progressively silenced, to complete the cellular maturation of the three myeloid lineages. In primary cells, abnormal ANKRD26 expression in committed progenitors directly affects the proliferation/differentiation balance for the three cell types. We show that ANKRD26 interacts with and crucially modulates the activity of MPL, EPOR and G-CSFR, three homodimeric type I cytokine receptors that regulate blood cell production. Higher than normal levels of ANKRD26 prevent the receptor internalization that leads to increased signaling and cytokine hypersensitivity. These findings afford evidence how ANKRD26 overexpression or the absence of its silencing during differentiation is responsible for myeloid blood cell abnormalities in patients with THC2.
Databáze:	MEDLINE
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