Progress in understanding the pathogenesis of Langerhans cell histiocytosis: back to Histiocytosis X?

Abstract:

:Langerhans cell histiocytosis (LCH), the most common histiocytic disorder, is characterized by the accumulation of CD1A(+) /CD207(+) 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.

journal_name

Br J Haematol

authors

Berres ML,Merad M,Allen CE

doi

10.1111/bjh.13247

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

3-13

issue

1

eissn

0007-1048

issn

1365-2141

journal_volume

169

pub_type

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