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Progress in understanding the pathogenesis of Langerhans cell histiocytosis: back to Histiocytosis X?
Author(s) -
Berres MarieLuise,
Merad Miriam,
Allen Carl E.
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13247
Subject(s) - langerhans cell histiocytosis , histiocyte , histiocytosis , myeloid , biology , langerhans cell , immunology , pathogenesis , pathology , dendritic cell , cancer research , medicine , immune system , disease
Summary Langerhans cell histiocytosis ( LCH ), the most common histiocytic disorder, is characterized by the accumulation of CD 1A + / CD 207 + mononuclear phagocytes within granulomatous lesions that can affect nearly all organ systems. Historically, LCH has been presumed to arise from transformed or pathologically activated epidermal dendritic cells called Langerhans cells. However, new evidence supports a model in which LCH occurs as a consequence of a misguided differentiation programme of myeloid dendritic cell precursors. Genetic, molecular and functional data implicate activation of the ERK signalling pathway at critical stages in myeloid differentiation as an essential and universal driver of LCH pathology. Based on these findings, we propose that LCH should be re‐defined as an inflammatory myeloid neoplasia . Increased understanding of LCH pathogenesis will provide opportunities to optimize and personalize therapy through improved risk‐stratification, targeted therapy and assessment of therapy response based on specific molecular features and origin of the pathological myeloid cells.