Langerhans cell histiocytosis: current advances in molecular pathogenesis

Tommaso Sconocchia; Johannes Foßelteder; Giuseppe Sconocchia; Andreas Reinisch

doi:10.3389/fimmu.2023.1275085

Langerhans cell histiocytosis: current advances in molecular pathogenesis

Front Immunol. 2023 Oct 26:14:1275085. doi: 10.3389/fimmu.2023.1275085. eCollection 2023.

Authors

Tommaso Sconocchia¹, Johannes Foßelteder¹, Giuseppe Sconocchia^#², Andreas Reinisch^#^{1

3}

Affiliations

¹ Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
² Institute of Translational Pharmacology, National Research Council (CNR), Rome, Italy.
³ Department of Blood Group Serology and Transfusion Medicine, Medical University of Graz, Graz, Austria.

^# Contributed equally.

Abstract

Langerhans cell histiocytosis (LCH) is a rare and clinically heterogeneous hematological disease characterized by the accumulation of mononuclear phagocytes in various tissues and organs. LCH is often characterized by activating mutations of the mitogen-activated protein kinase (MAPK) pathway with BRAF^V600E being the most recurrent mutation. Although this discovery has greatly helped in understanding the disease and in developing better investigational tools, the process of malignant transformation and the cell of origin are still not fully understood. In this review, we focus on the newest updates regarding the molecular pathogenesis of LCH and novel suggested pathways with treatment potential.

Keywords: BRAFV600E; MAP2K1; dendritic cells; langerhans cell histiocytosis; monocytes; oncogene; senescence.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Gain of Function Mutation
Histiocytosis, Langerhans-Cell* / genetics
Histiocytosis, Langerhans-Cell* / therapy
Humans
Mitogen-Activated Protein Kinases / genetics
Mutation
Proto-Oncogene Proteins B-raf* / genetics
Proto-Oncogene Proteins B-raf* / metabolism

Substances

Proto-Oncogene Proteins B-raf
Mitogen-Activated Protein Kinases

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. GS is supported by the Italian Association for Cancer Research (AIRC; Investigator Grant 2020-24440), and the European Union, European Fund for Regional Development, MUR-PON: Unit IFT, Grant TITAN 2021-ARS01_00906. AR is supported by the Austrian Science Fund (number P32783 and I5021), the Austrian Society of Internal Medicine (Joseph Skoda Fellowship), the Austrian Society of Hematology and Oncology (Clinical Research Grant), and MEFOgraz.