Statistics from Altmetric.com
Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, characterised by tissue infiltration by foamy CD68+ CD1a− histiocytes.1 The disease has pleomorphic clinical manifestations, including long bones and extraskeletal involvement, and may be life-threatening, particularly when heart and central nervous system are affected.1
ECD histiocytes secrete proinflammatory cytokines2 and carry activating mutations along the RAS-RAF-MEK-ERK protein kinase signalling pathway, most commonly the BRAFV600E oncogenic mutation.3 4 Accordingly, patients with ECD have been treated with cytokine inhibitors, including infliximab,⇓ 5 and, more recently, with the BRAFV600E inhibitor vemurafenib.6 The latter, however, induces sustained but partial clinical responses and recurrences on discontinuation,6 underlining the need for more effective therapeutic strategies.
To identify the outcomes downstream constitutive ERK phosphorylation in ECD histiocytes and their response to small molecule-based inhibition, we performed three-dimensional (3D) culture of tissues from three BRAFV600E-mutated ECD patients in the RCCS bioreactor7 (and online supplementary methods) in the presence/absence of vemurafenib or infliximab, used as control.
All patient samples maintained production of prototypical cytokines and chemokines2 in bioreactor, thus validating this technology also for ECD; moreover, infliximab, and, to a lesser degree, vemurafenib, significantly decreased cyto-chemokines and …
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.