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3 "Langerhans cell histiocytosis"
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Original Article
Unraveling the Genetic Landscape of Langerhans Cell Histiocytosis in Korean Patients: Comprehensive Insights from Mutational Profiles and Clinical Correlations
Kyung-Nam Koh, Ha Ra Jun, Ji-Young Lee, Ji Young Kim, Su Hyun Yoon, Young Kwon Koh, Sung Han Kang, Hyery Kim, Ho Joon Im, Sung-Min Chun
Received August 14, 2024  Accepted December 22, 2024  Published online December 24, 2024  
DOI: https://doi.org/10.4143/crt.2024.782    [Accepted]
AbstractAbstract PDF
Purpose
This study aimed to conduct a comprehensive genetic analysis of patients with Langerhans cell histiocytosis (LCH), focusing on the frequency of MAPK pathway mutations, detailed mutation profiles of MAPK pathway genes, and their correlation with clinical features and prognosis in Korean LCH patients.
Materials and Methods
We performed targeted next-generation sequencing, capable of capturing exons from 382 cancer-related genes, on genomic DNA extracted from formaldehyde-fixed and paraffin-embedded samples of 45 pathologically confirmed LCH patients.
Results
The majority of patients (91.1%) exhibited single-system disease, with bone being the most common location (84.4%). Initial treatments varied, and no patients died during a median follow-up of 6.8 years. Our genetic assays revealed that all patients had MAPK pathway alterations, including BRAF mutations in 51.2%, MAP2K1 mutations in 42.2%, RAF1 mutations in 4.4%, and a KRAS mutation in 2.2%. These mutations were mutually exclusive. Detailed mutation profiles indicated that among the BRAF mutations, there were 18 point mutations and 5 in-frame deletions, while most MAP2K1 mutations were in-frame deletions, with only one missense mutation. We detected previously unreported variations of point mutations in BRAF, MAP2K1, KRAS, and the first instance of a RAF1-KLC1 fusion in LCH. MAP2K1 mutations occurred more frequently in older patients, whereas BRAF V600 mutations were commonly associated with unifocal bone disease. Genetic mutations did not correlate with high-risk features or event-free survival.
Conclusion
This study identified mutually exclusive MAPK pathway mutations in every LCH patient through comprehensive genetic analysis, highlighting the importance of inclusive testing in understanding the disease's genetics.
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Case Report
Case Report of Erdheim-Chester Disease Successfully Treated with Pegylated Interferon: A Single-Center Experience
Yujin Lim, Sang Eun Yoon, Junhun Cho, Darae Kim, Chul Won Jung
Cancer Res Treat. 2023;55(3):1053-1057.   Published online January 19, 2023
DOI: https://doi.org/10.4143/crt.2022.1535
AbstractAbstract PDFPubReaderePub
Erdheim-Chester disease (ECD), also known as non-Langerhans cell histiocytosis, is a multi-systemic disease with unclear pathogenesis. Based on a small number of case studies, pegylated interferon-α (PEG-IFN-α) has been used as the front-line treatment option. However, there are limited data regarding administration of ropegylated-interferon α-2b (ROPEG-IFN-α 2b) for ECD patients. Herein, we report two cases of severe ECD treated with two types of PEG-IFN-α. One patient with heart and skeleton involvement and BRAF V600E mutation was treated with weekly PEG-IFN-α 2a. Another patient with bone involvement and no BRAF V600E mutation was administered monthly ROPEG-IFN-α 2b. The two types of PEG-IFN-α showed excellent disease control, excellent survival outcomes, and manageable toxicities in ECD patients. These results suggest that ROPEG-IFN-α 2b could be used equivalently to PEG-IFN-α 2a for management of advanced ECD.

Citations

Citations to this article as recorded by  
  • An Autopsied Case of Erdheim-Chester Disease with Severe Cardiovascular Involvement
    Atsushi Matsunashi, Wang Zhipeng, Akihiko Sugimoto, Masakazu Fujimoto, Akihiko Yoshizawa, Ryo Sakamoto, Michihiro Uyama, Kohei Ikezoe, Kiminobu Tanizawa, Tomohiro Handa, Toyohiro Hirai
    Internal Medicine.2025;[Epub]     CrossRef
  • Recent advances in therapeutic strategies of Erdheim-Chester disease
    Rohit Doke, Rahul Lokhande, Kalyani Chande, Kuldeep Vinchurkar, Bhupendra G. Prajapati
    Naunyn-Schmiedeberg's Archives of Pharmacology.2025;[Epub]     CrossRef
  • Erdheim–Chester disease: Comprehensive insights from genetic mutations to clinical manifestations and therapeutic advances
    Rishabh Chaudhary, Anand Kumar, Alpana Singh, Vipul Agarwal, Mujeeba Rehman, Arjun Singh Kaushik, Siddhi Srivastava, Sukriti Srivastava, Vikas Mishra
    Disease-a-Month.2025; : 101845.     CrossRef
  • Advances in Understanding and Management of Erdheim-Chester Disease
    Aniruddha Murahar Kulkarni, Prasanna Kumar Reddy Gayam, Jesil Mathew Aranjani
    Life Sciences.2024; 348: 122692.     CrossRef
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Original Article
Pediatric cancer
Effectiveness and Safety of Dabrafenib in the Treatment of 20 Chinese Children with BRAFV600E-Mutated Langerhans Cell Histiocytosis
Ying Yang, Dong Wang, Lei Cui, Hong-Hao Ma, Li Zhang, Hong-Yun Lian, Qing Zhang, Xiao-Xi Zhao, Li-Ping Zhang, Yun-Ze Zhao, Na Li, Tian-You Wang, Zhi-Gang Li, Rui Zhang
Cancer Res Treat. 2021;53(1):261-269.   Published online September 15, 2020
DOI: https://doi.org/10.4143/crt.2020.769
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We sought to investigate the effectiveness and safety of dabrafenib in children with BRAFV600E-mutated Langerhans cell histiocytosis (LCH).
Materials and Methods
A retrospective analysis was performed on 20 children with BRAFV600E-mutated LCH who were treated with dabrafenib.
Results
The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)+ group and six patients (30%) in the RO group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAFV600E (cfBRAFV600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients.
Conclusion
Some children with BRAFV600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.

Citations

Citations to this article as recorded by  
  • Genetic Landscape and Its Prognostic Impact in Children With Langerhans Cell Histiocytosis
    Chan-Juan Wang, Lei Cui, Shuang-Shuang Li, Hong-Hao Ma, Dong Wang, Hong-Yun Lian, Yun-Ze Zhao, Li-Ping Zhang, Wei-Jing Li, Qing Zhang, Xiao-Xi Zhao, Ying Yang, Xiao-Tong Huang, Wei Liu, Yi-Zhuo Wang, Wan-Shui Wu, Tian-You Wang, Rui Zhang, Zhi-Gang Li
    Archives of Pathology & Laboratory Medicine.2025; 149(2): 175.     CrossRef
  • Targeted therapy and immunotherapy for orbital and periorbital tumors: a major review
    Emmanuel Lee Boniao, Richard C. Allen, Gangadhara Sundar
    Orbit.2024; 43(5): 656.     CrossRef
  • Treatment of children with refractory/relapse high risk langerhans cell histiocytosis with the combination of cytarabine, vindesine and prednisone
    Wenqian Wang, Jian Ge, Honghao Ma, Hongyun Lian, Lei Cui, Yunze Zhao, Zhigang Li, Tianyou Wang, Rui Zhang
    BMC Pediatrics.2024;[Epub]     CrossRef
  • Vemurafenib combined with chemotherapy achieved sustained remission in pediatric LCH: a multi-center observational study
    Jiaying Lei, Wenxia Wang, Danna Lin, Chengguang Zhu, Wenguang Jia, Wenjun Weng, Xiaoshan Liu, Yuhan Ma, Zhixuan Wang, Lihua Yang, Xiangling He, Yunyan He, Yang LI
    Journal of Cancer Research and Clinical Oncology.2024;[Epub]     CrossRef
  • Clinical features and treatment outcomes of liver involvement in paediatric Langerhans cell histiocytosis
    Xinshun Ge, Wenxin Ou, Ang Wei, Hongyun Lian, Honghao Ma, Lei Cui, Dong Wang, Liping Zhang, Xiaoman Wang, Lejian He, Rui Zhang, Tianyou Wang
    BMC Pediatrics.2024;[Epub]     CrossRef
  • Refractory juvenile xanthogranuloma of the mastoid bone responsive to trametinib
    Isaac Hauk, Ignacio Gonzalez‐Gomes, Deepak Chellapandian, Jonathan Metts, Peter H. Shaw
    Pediatric Blood & Cancer.2024;[Epub]     CrossRef
  • Advancements in the understanding and management of histiocytic neoplasms
    Kyung-Nam Koh, Su Hyun Yoon, Sung Han Kang, Hyery Kim, Ho Joon Im
    Blood Research.2024;[Epub]     CrossRef
  • Real-world experience with targeted therapy in patients with histiocytic neoplasms in the Netherlands and in Belgium
    Paul G. Kemps, F. J. Sherida H. Woei-A-Jin, Patrick Schöffski, Thomas Tousseyn, Isabelle Vanden Bempt, Friederike A. G. Meyer-Wentrup, Natasja Dors, Natasha K. A. van Eijkelenburg, Marijn A. Scheijde-Vermeulen, Ingrid M. Jazet, Maarten Limper, Margot Jak,
    Blood Neoplasia.2024; 1(3): 100023.     CrossRef
  • The clinical impact of serum soluble CD25 levels in children with Langerhans cell histiocytosis
    Zi-Jing Zhao, Hong-Yun Lian, Wei-Jing Li, Qing Zhang, Hong-Hao Ma, Dong Wang, Yun-Ze Zhao, Ting Zhu, Hua-Lin Li, Xiao-Tong Huang, Tian-You Wang, Rui Zhang, Lei Cui, Zhi-Gang Li
    Jornal de Pediatria.2024;[Epub]     CrossRef
  • Liver transplantation in a child with sclerosing cholangitis due to Langerhans cell histiocytosis: a case report
    Xue-Lian Wang, Chun-Xiao Fang, Min-Xia Chen, Hua-Mei Yang, Lan-Hui She, Yu Gong, Yi Xu, Wei-Qiang Xiao, Jin-Sheng Tian, Bin Ai, Li Huang, Xu-Fang Li
    Frontiers in Pediatrics.2024;[Epub]     CrossRef
  • BRAF V600E gene mutation is present in primary intraosseous Rosai-Dorfman disease
    Lokman Cevik, Swati Satturwar, Dan Jones, Joel Mayerson, Steve Oghumu, O. Hans Iwenofu
    Human Pathology.2024; 154: 105702.     CrossRef
  • Langerhans cell histiocytosis as a clonal disease of mononuclear phagocyte system
    Evgeniy F. Khynku, Maria K. Monaenkova, Olga B. Tamrazova, Alexey V. Taganov, Мarina А. Gureeva, Gayane E. Bagramova, Anton V. Molochkov
    Almanac of Clinical Medicine.2023; 50(7): 428.     CrossRef
  • Lineage switching of the cellular distribution of BRAF V600E in multisystem Langerhans cell histiocytosis
    Paul Milne, Simon Bomken, Olga Slater, Ashish Kumar, Adam Nelson, Somak Roy, Jessica Velazquez, Kshitij Mankad, James Nicholson, Dan Yeomanson, Richard Grundy, Ahmed Kamal, Anthony Penn, Jane Pears, Gerard Millen, Bruce Morland, James Hayden, Jason Lam, M
    Blood Advances.2023; 7(10): 2171.     CrossRef
  • Treatment of Langerhans Cell Histiocytosis and Histiocytic Disorders: A Focus on MAPK Pathway Inhibitors
    Ashley V. Geerlinks, Oussama Abla
    Pediatric Drugs.2023; 25(4): 399.     CrossRef
  • Dabrafenib, alone or in combination with trametinib, in BRAF V600–mutated pediatric Langerhans cell histiocytosis
    James A. Whitlock, Birgit Geoerger, Ira J. Dunkel, Michael Roughton, Jeea Choi, Lisa Osterloh, Mark Russo, Darren Hargrave
    Blood Advances.2023; 7(15): 3806.     CrossRef
  • Therapiestrategien bei Kindern und Jugendlichen mit Langerhanszell Histiozytosen
    Anke Elisabeth Barnbrock, Caroline Hutter, Konrad Bochennek, Milen Minkov, Thomas Lehrnbecher
    Klinische Pädiatrie.2023; 235(06): 342.     CrossRef
  • Mutant PIK3CA is a targetable driver alteration in histiocytic neoplasms
    Benjamin H. Durham, Oshrat Hershkovitz-Rokah, Omar Abdel-Wahab, Mariko Yabe, Young Rock Chung, Gilad Itchaki, Maayan Ben-Sasson, Vered A. Asher-Guz, David Groshar, Seyram A. Doe-Tetteh, Tina Alano, David B. Solit, Ofer Shpilberg, Eli L. Diamond, Roei D. M
    Blood Advances.2023; 7(23): 7319.     CrossRef
  • Validation of Liquid Chromatography Coupled with Tandem Mass Spectrometry for the Determination of 12 Tyrosine Kinase Inhibitors (TKIs) and Their Application to Therapeutic Drug Monitoring in Adult and Pediatric Populations
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    Pharmaceutics.2023; 16(1): 5.     CrossRef
  • Langerhans cell histiocytosis: promises and caveats of targeted therapies in high-risk and CNS disease
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    Hematology.2023; 2023(1): 386.     CrossRef
  • Characteristics and Treatment Outcomes of Pediatric Langerhans Cell Histiocytosis with Thymic Involvement
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    The Journal of Pediatrics.2022; 244: 194.     CrossRef
  • Clinical features and treatment outcomes of pediatric Langerhans cell histiocytosis with macrophage activation syndrome-hemophagocytic lymphohistiocytosis
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    Orphanet Journal of Rare Diseases.2022;[Epub]     CrossRef
  • Current perspectives on the role of liver transplantation for Langerhans cell histiocytosis: A narrative review
    Jagadeesh Menon, Ashwin Rammohan, Mukul Vij, Naresh Shanmugam, Mohamed Rela
    World Journal of Gastroenterology.2022; 28(30): 4044.     CrossRef
  • Research Progress of BRAF V600E Gene Mutation in Papillary Thyroid Carcinoma
    延泽 刘
    Advances in Clinical Medicine.2022; 12(09): 8499.     CrossRef
  • Recent advances in the understanding of the molecular pathogenesis and targeted therapy options in Langerhans cell histiocytosis
    Jin Kyung Suh, Sunghan Kang, Hyery Kim, Ho Joon Im, Kyung-Nam Koh
    BLOOD RESEARCH.2021; 56(S1): S65.     CrossRef
  • Improvement in Pituitary Imaging After Targeted Therapy in Three Children with BRAF-Mutated Langerhans Cell Histiocytosis with Pituitary Involvement


    Ying Yang, Dong Wang, Na Li, Honghao Ma, Hongyun Lian, Lei Cui, Qing Zhang, Xiaoxi Zhao, Liping Zhang, Yunze Zhao, Chanjuan Wang, Li Zhang, Tianyou Wang, Zhigang Li, Rui Zhang
    OncoTargets and Therapy.2020; Volume 13: 12357.     CrossRef
  • 34,905 View
  • 236 Download
  • 19 Web of Science
  • 25 Crossref
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