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Functional evidence for derivation of systemic histiocytic neoplasms from hematopoietic stem/progenitor cells.
- Source :
-
Blood [Blood] 2017 Jul 13; Vol. 130 (2), pp. 176-180. Date of Electronic Publication: 2017 May 31. - Publication Year :
- 2017
-
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 CD34 <superscript>+</superscript> cells from patients with ECD and LCH/ECD, including detection of shared origin of LCH and acute myelomonocytic leukemia driven by TET2 -mutant CD34 <superscript>+</superscript> cell progenitors in one patient. We also demonstrate functional self-renewal capacity for CD34 <superscript>+</superscript> 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.<br /> (© 2017 by The American Society of Hematology.)
- Subjects :
- Adult
Alleles
Animals
Antigens, CD34 genetics
Antigens, CD34 immunology
Bone Marrow Cells immunology
Bone Marrow Transplantation
Cell Differentiation
DNA-Binding Proteins immunology
Dendritic Cells immunology
Dendritic Cells pathology
Dioxygenases
Erdheim-Chester Disease genetics
Erdheim-Chester Disease immunology
Gene Expression
Hematopoietic Stem Cells immunology
Histiocytosis, Langerhans-Cell genetics
Histiocytosis, Langerhans-Cell immunology
Humans
Immunophenotyping
Macrophages immunology
Macrophages pathology
Mice
Monocytes immunology
Monocytes pathology
Mutation
Proto-Oncogene Proteins immunology
Proto-Oncogene Proteins B-raf immunology
Transplantation, Heterologous
Bone Marrow Cells pathology
DNA-Binding Proteins genetics
Erdheim-Chester Disease pathology
Hematopoietic Stem Cells pathology
Histiocytosis, Langerhans-Cell pathology
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins B-raf genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 130
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 28566492
- Full Text :
- https://doi.org/10.1182/blood-2016-12-757377