Functional evidence for derivation of systemic histiocytic neoplasms from hematopoietic stem/progenitor cells

Benjamin H. Durham, Damien Roos-Weil, Claude Baillou, Fleur Cohen-Aubart, Akihide Yoshimi, Makoto Miyara, Matthias Papo, Zofia Hélias-Rodzewicz, Nathalie Terrones, Neval Ozkaya, Ahmet Dogan, Raajit Rampal, Fanny Urbain, Lucie Le Fèvre, Eli L. Diamond, Christopher Y. Park, Thomas Papo, Frédéric Charlotte, Guy Gorochov, Valérie TalyOlivier A. Bernard, Zahir Amoura, Omar Abdel-Wahab, François M. Lemoine, Julien Haroche, Jean François Emile

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    95 Citations (Scopus)

    Résumé

    Langerhans cell histiocytosis (LCH) and the non-LCH neoplasm Erdheim-Chester disease (ECD) are heterogeneous neoplastic disorders marked by infiltration of pathologic macrophage-, dendritic cell–, or monocyte-derived cells in tissues driven by recurrent mutations activating MAPK signaling. Although recent data indicate that at least a proportion of LCH and ECD patients have detectable activating kinase mutations in circulating hematopoietic cells and bone marrow–based hematopoietic progenitors, functional evidence of the cell of origin of histiocytosis from actual patient materials has long been elusive. Here, we provide evidence for mutations in MAPK signaling intermediates in CD341 cells from patients with ECD and LCH/ECD, including detection of shared origin of LCH and acute myelomonocytic leukemia driven by TET2-mutant CD341 cell progenitors in one patient. We also demonstrate functional self-renewal capacity for CD341 cells to drive the development of histiocytosis in xenotransplantation assays in vivo. These data indicate that the cell of origin of at least a proportion of patients with systemic histiocytoses resides in hematopoietic progenitor cells prior to committed monocyte/macrophage or dendritic cell differentiation and provide the first example of a patient-derived xenotransplantation model for a human histiocytic neoplasm.

    langue originaleAnglais
    Pages (de - à)176-180
    Nombre de pages5
    journalBlood
    Volume130
    Numéro de publication2
    Les DOIs
    étatPublié - 13 juil. 2017

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