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


Authors: Durham, B. H.; Roos-Weil, D.; Baillou, C.; Cohen-Aubart, F.; Yoshimi, A.; Miyara, M.; Papo, M.; Hélias-Rodzewicz, Z.; Terrones, N.; Ozkaya, N.; Dogan, A.; Rampal, R.; Urbain, F.; Fèvre, L. L.; Diamond, E. L.; Park, C. Y.; Papo, T.; Charlotte, F.; Gorochov, G.; Taly, V.; Bernard, O. A.; Amoura, Z.; Abdel-Wahab, O.; Lemoine, F. M.; Haroche, J.; Emile, J. F.
Article Title: Functional evidence for derivation of systemic histiocytic neoplasms from hematopoietic stem/progenitor cells
Abstract: 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. © 2017 by The American Society of Hematology.
Journal Title: Blood
Volume: 130
Issue: 2
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2017-07-13
Start Page: 176
End Page: 180
Language: English
DOI: 10.1182/blood-2016-12-757377
PROVIDER: scopus
PUBMED: 28566492
PMCID: PMC5510787
DOI/URL:
Notes: Article -- Export Date: 2 August 2017 -- Source: Scopus
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MSK Authors
  1. Raajit Kumar Rampal
    128 Rampal
  2. Eli Louis Diamond
    83 Diamond
  3. Ahmet Dogan
    166 Dogan
  4. Benjamin Heath Durham
    60 Durham
  5. Neval   Ozkaya
    18 Ozkaya
  6. Akihide   Yoshimi
    22 Yoshimi