Elucidated pathogenesis and therapeutic prospects in Langerhans cell histiocytosis

  • MORIMOTO Akira
    Department of Pediatrics, Jichi Medical University School of Medicine
  • SHIODA Yoko
    Children’s Cancer Center, National Center for Child Health and Development
  • SAKAMOTO Kenichi
    Department of Pediatrics, Shiga University of Medical Science
  • KUDO Ko
    Department of Pediatrics, Hirosaki University Graduate School of Medicine
  • IMAMURA Toshihiko
    Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
  • KUDO Kazuko
    Department of Pediatrics, Fujita Health University

Bibliographic Information

Other Title
  • ランゲルハンス細胞組織球症における病態解明と治療の展望

Search this article

Description

<p>Langerhans cell histiocytosis (LCH) is characterized by immature dendritic cell proliferation, which is currently classified as an inflammatory myeloid neoplasm. Clinical features and outcomes vary from spontaneously regressing isolated bone disease to fatal liver, spleen, or hematopoietic system (risk organ) involvement-positive multisystem disease. LCH cells have the only mutation in the mitogen-activated protein kinase (MAPK) signaling pathway gene, represented by the BRAF V600E mutation, which is the driver mutation. The type of disease depends on the stage of hematopoietic cell differentiation at which the mutation occurs. LCH cells acquire anti-apoptosis and senescence-associated secretory phenotype by oncogene-induced senescence, with migration failure to lymph nodes. These cause LCH cell accumulation and various inflammatory cell recruitment in the lesion, resulting in severe inflammation. Tissue damage in LCH is due to this inflammation, not the LCH cell proliferation. Patients with a risk of organ involvement without the initial treatment response may be rescued by allogeneic hematopoietic stem cell transplantation after reducing the disease activity with MAPK inhibitors. Intravenous zoledronic acid and intrathecal cytarabine injections have been introduced into the ongoing clinical trial in Japan to reduce bone recurrence and prevent neurodegeneration as sequelae.</p>

Journal

  • Rinsho Ketsueki

    Rinsho Ketsueki 63 (5), 373-382, 2022

    The Japanese Society of Hematology

Related Projects

See more

Details 詳細情報について

  • CRID
    1390573792574606848
  • DOI
    10.11406/rinketsu.63.373
  • ISSN
    18820824
    04851439
  • PubMed
    35662160
  • Text Lang
    ja
  • Article Type
    journal article
  • Data Source
    • JaLC
    • PubMed
    • KAKEN
  • Abstract License Flag
    Disallowed

Report a problem

Back to top