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Hematopoietic origin of Langerhans cell histiocytosis and Erdheim-Chester disease in adults.
Milne, Paul; Bigley, Venetia; Bacon, Chris M; Néel, Antoine; McGovern, Naomi; Bomken, Simon; Haniffa, Muzlifah; Diamond, Eli L; Durham, Benjamin H; Visser, Johannes; Hunt, David; Gunawardena, Harsha; Macheta, Mac; McClain, Kenneth L; Allen, Carl; Abdel-Wahab, Omar; Collin, Matthew.
Affiliation
  • Milne P; Institute of Cellular Medicine and.
  • Bigley V; Institute of Cellular Medicine and.
  • Bacon CM; Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Néel A; Department of Cellular Pathology, Newcastle upon Tyne Hospitals National Health Service Foundation Trust, Newcastle upon Tyne, United Kingdom.
  • McGovern N; Internal Medicine Department, Hôtel-Dieu University Hopital, Nantes, France.
  • Bomken S; Institute of Cellular Medicine and.
  • Haniffa M; Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom.
  • Diamond EL; Institute of Cellular Medicine and.
  • Durham BH; Memorial Sloan Kettering Cancer Center, New York, NY.
  • Visser J; Memorial Sloan Kettering Cancer Center, New York, NY.
  • Hunt D; East Midlands Children's and Young Persons' Integrated Cancer Service, Leicester Children's Hospital, Leicester, United Kingdom.
  • Gunawardena H; Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
  • Macheta M; Rheumatology Department, North Bristol National Health Service Trust, Bristol, United Kingdom.
  • McClain KL; Blackpool Teaching Hospitals National Health Service Foundation Trust, Blackpool, United Kingdom; and.
  • Allen C; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.
  • Abdel-Wahab O; Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX.
  • Collin M; Memorial Sloan Kettering Cancer Center, New York, NY.
Blood ; 130(2): 167-175, 2017 07 13.
Article in En | MEDLINE | ID: mdl-28512190
Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) are rare histiocytic disorders induced by somatic mutation of MAPK pathway genes. BRAFV600E mutation is the most common mutation in both conditions and also occurs in the hematopoietic neoplasm hairy cell leukemia (HCL). It is not known if adult LCH or ECD arises from hematopoietic stem cells (HSCs), nor which potential blood borne precursors lead to the formation of histiocytic lesions. In this study, BRAFV600E allele-specific polymerase chain reaction was used to map the neoplastic clone in 20 adults with LCH, ECD, and HCL. BRAFV600E was tracked to classical monocytes, nonclassical monocytes, and CD1c+ myeloid dendritic cells (DCs) in the blood, and mutations were observed in HSCs and myeloid progenitors in the bone marrow of 4 patients. The pattern of involvement of peripheral blood myeloid cells was indistinguishable between LCH and ECD, although the histiocytic disorders were distinct to HCL. As reported in children, detection of BRAFV600E in peripheral blood of adults was a marker of active multisystem LCH. The healthy counterparts of myeloid cells affected by BRAF mutation had a range of differentiation potentials depending on exogenous signals. CD1c+ DCs acquired high langerin and CD1a with granulocyte-macrophage colony-stimulating factor and transforming growth factor ß alone, whereas CD14+ classical monocytes required additional notch ligation. Both classical and nonclassical monocytes, but not CD1c+ DCs, made foamy macrophages easily in vitro with macrophage colony-stimulating factor and human serum. These studies are consistent with a hematopoietic origin and >1 immediate cellular precursor in both LCH and ECD.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bone Marrow Cells / Hematopoietic Stem Cells / Histiocytosis, Langerhans-Cell / Erdheim-Chester Disease / Proto-Oncogene Proteins B-raf Type of study: Diagnostic_studies Language: En Journal: Blood Year: 2017 Document type: Article Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bone Marrow Cells / Hematopoietic Stem Cells / Histiocytosis, Langerhans-Cell / Erdheim-Chester Disease / Proto-Oncogene Proteins B-raf Type of study: Diagnostic_studies Language: En Journal: Blood Year: 2017 Document type: Article Country of publication: United States