Toggle Main Menu Toggle Search

Open Access padlockePrints

Hematopoietic origin of Langerhans cell histiocytosis and Erdheim Chester disease in adults

Lookup NU author(s): Dr Paul Milne, Dr Venetia BigleyORCiD, Dr Christopher Bacon, Dr Naomi McGovern, Dr Simon BomkenORCiD, Professor Muzlifah Haniffa, Professor Matthew CollinORCiD



This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Society of Hematology, 2017.

For re-use rights please refer to the publisher's terms and conditions.


Langerhans cell histiocytosis (LCH) and Erdheim Chester Disease (ECD) are rare histiocytic disorders induced by somatic mutation of MAP kinase pathway genes. BRAF(V600E) 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 arise from hematopoietic stem cells (HSC) nor which potential blood borne precursors lead to the formation of histiocytic lesions. In this study, BRAF V600E allele-specific PCR was used to map the neoplastic clone in 20 adults with LCH ECD and HCL. BRAF(V600E) was tracked to classical monocytes, non-classical monocytes and CD1c+ myeloid 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 BRAF(V600E) in peripheral blood of adults was a marker of active multi-system LCH (MS-LCH). The healthy counterparts of myeloid cells affected by BRAF mutation had a range of differentiation potentials depending upon exogenous signals. CD1c+ DCs acquired high langerin and CD1a with GM-CSF and TGFβ alone while CD14+ classical monocytes required additional notch ligation. Both classical and non-classical monocytes, but not CD1c+ DCs made foamy macrophages easily in vitro with M-CSF and human serum (HS). These studies are consistent with a hematopoietic origin and more than one immediate cellular precursor, in both LCH and ECD.

Publication metadata

Author(s): Milne P, Bigley V, Bacon CM, Néel A, McGovern N, Bomken S, Haniffa M, Diamond EL, Durham BH, Visser J, Hunt D, Gunawardena H, Macheta M, McClain KL, Allen C, Abdel-Wahab O, Collin M

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2017

Volume: 130

Issue: 2

Pages: 167-175

Print publication date: 13/07/2017

Online publication date: 16/05/2017

Acceptance date: 24/04/2017

Date deposited: 21/06/2017

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology


DOI: 10.1182/blood-2016-12-757823

PubMed id: 28512190


Altmetrics provided by Altmetric


Funder referenceFunder name
101155/Z/13/ZWellcome Trust
C30484/A21025Cancer Research UK CRUK (open competition)