Details of Disease

General Information of Disease (ID: DISDQSW3)

• Disease Name: Langerhans cell histiocytosis
• Synonyms: Lch; Langerhans-cell histiocytosis; letterer-Siwe disease of lymph nodes of inguinal region and/or lower limb; letterer-Siwe disease involving intrathoracic lymph nodes; letterer-Siwe disease involving lymph nodes of head, face and neck; letterer-Siwe disease involving intra-abdominal lymph nodes; letterer-Siwe disease of lymph nodes of head, face and neck; Langerhans cell granulomatosis; letterer-Siwe disease involving lymph nodes of head, face, and neck; letterer-Siwe disease involving intrapelvic lymph nodes; Langerhan's cell histiocytosis; letterer-Siwe disease of lymph nodes of axilla and upper limb; letterer-Siwe disease of intra-abdominal lymph nodes; letterer-Siwe disease of lymph nodes of inguinal region and lower limb; Langerhans cell histiocytosis, NOS; letterer-Siwe disease of spleen; letterer-Siwe disease of intrapelvic lymph nodes; letterer-Siwe disease involving lymph nodes of multiple sites; histiocytosis X; letterer-Siwe disease of intrathoracic lymph nodes; letterer-Siwe disease of lymph nodes of axilla and/or upper limb; letterer-Siwe disease of lymph nodes of multiple sites; letterer-Siwe disease of lymph nodes of inguinal region amd/or lower limb; letterer-Siwe disease involving lymph nodes of axilla and upper limb; letterer-Siwe disease involving lymph nodes of inguinal region and lower limb; LCH; Langerhans cell histiocytosis; letterer-Siwe disease of lymph nodes of head, face and/or neck; letterer-Siwe disease involving spleen; Langerhans cell histiocytosis, Not otherwise specified
• Definition: Langerhans cell histiocytosis (LCH) is a systemic disease associated with the proliferation and accumulation (usually in granulomas) of Langerhans cells in various tissues.|We follow NCIT in classifying this as a neoplasm but this may be revisited
• Disease Hierarchy:
  DISA03DD: Phagocytic cell dysfunction
  DISG6V5T: Dendritic cell tumor
  DISIYLND: Histiocytosis
  DIS17G9I: Leukocyte disorder
  DISDQSW3: Langerhans cell histiocytosis
• Disease Identifiers:
  MONDO ID: MONDO_0018310
  MESH ID: D006646
  UMLS CUI: C0019621
  OMIM ID: 604856
  MedGen ID: 5568
  Orphanet ID: 389
  SNOMED CT ID: 110450007

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Clofarabine	DMCVJ86	Approved	Small molecular drug	[1]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 14 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ARAF	TT5TURO	Limited	Genetic Variation	[2]
BRAF	TT0EOB8	Limited	Genetic Variation	[3]
GNAQ	TTL1SRG	moderate	Genetic Variation	[4]
CD83	TTT9MRQ	Strong	Altered Expression	[5]
EPHB2	TTKPV6O	Strong	Altered Expression	[6]
FSHR	TTZFDBT	Strong	Genetic Variation	[7]
JAG2	TTOJY1B	Strong	Altered Expression	[8]
LHCGR	TT2O4W9	Strong	Genetic Variation	[9]
MAP2K1	TTIDAPM	Strong	Genetic Variation	[10]
MAP2K7	TT6QY3J	Strong	Altered Expression	[6]
SOST	TTYRO4F	Strong	Biomarker	[11]
STAB1	TTJFEOC	Strong	Biomarker	[12]
GNA11	TTSRXJW	Definitive	Genetic Variation	[4]
OAT	TTTSCQ2	Definitive	Biomarker	[13]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC29A3	DTZAWTH	Strong	Genetic Variation	[14]

This Disease Is Related to 4 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
KIR2DL4	OTXN18OA	moderate	Altered Expression	[15]
PLEKHA6	OTALCXKW	moderate	Biomarker	[6]
GNA14	OTYZ1ZI0	Strong	Genetic Variation	[16]
INSL3	OT7KUNTE	Strong	Biomarker	[17]

References

• [1] Clofarabine FDA Label
• [2] Treatment of Langerhans cell histiocytosis: role of BRAF/MAPK inhibition.Hematology Am Soc Hematol Educ Program. 2015;2015:565-70. doi: 10.1182/asheducation-2015.1.565.
• [3] BRAF gene mutations in synchronous papillary thyroid carcinoma and Langerhans cell histiocytosis co-existing in the thyroid gland: a case report and literature review.BMC Cancer. 2019 Feb 22;19(1):170. doi: 10.1186/s12885-019-5372-3.
• [4] WHO 2016 classification: changes and advancements in the diagnosis of miscellaneous primary CNS tumours.Neuropathol Appl Neurobiol. 2018 Feb;44(2):163-171. doi: 10.1111/nan.12397.
• [5] BRAFV600E and MAP2K1 mutations in Langerhans cell histiocytosis occur predominantly in children.Hematol Oncol. 2017 Dec;35(4):845-851. doi: 10.1002/hon.2344. Epub 2016 Sep 6.
• [6] A novel fusion gene PLEKHA6-NTRK3 in langerhans cell histiocytosis.Int J Cancer. 2019 Jan 1;144(1):117-124. doi: 10.1002/ijc.31636. Epub 2018 Oct 26.
• [7] Molecular genetic, biochemical, and clinical implications of gonadotropin receptor mutations.Mol Genet Metab. 1998 Feb;63(2):75-84. doi: 10.1006/mgme.1997.2650.
• [8] JAG2 signaling induces differentiation of CD14(+) monocytes into Langerhans cell histiocytosis-like cells.J Leukoc Biol. 2019 Jan;105(1):101-111. doi: 10.1002/JLB.1A0318-098R. Epub 2018 Oct 8.
• [9] Novel compound heterozygous variants in the LHCGR gene identified in a subject with Leydig cell hypoplasia type 1.J Pediatr Endocrinol Metab. 2018 Jan 26;31(2):239-245. doi: 10.1515/jpem-2016-0445.
• [10] Pediatric Langerhans cell histiocytosis: the impact of mutational profile on clinical progression and late sequelae.Ann Hematol. 2019 Jul;98(7):1617-1626. doi: 10.1007/s00277-019-03678-y. Epub 2019 Mar 28.
• [11] Bone metabolism in Langerhans cell histiocytosis.Endocr Connect. 2018 Jul;7(7):R246-R253. doi: 10.1530/EC-18-0186. Epub 2018 Jul 2.
• [12] Expression of stabilin-1 in M2 macrophages in human granulomatous disease and melanocytic lesions.Int J Clin Exp Pathol. 2014 Mar 15;7(4):1625-34. eCollection 2014.
• [13] Increased expression of growth factor genes for macrophages and fibroblasts in bronchoalveolar lavage cells of a patient with pulmonary histiocytosis X.Thorax. 1991 Nov;46(11):835-8. doi: 10.1136/thx.46.11.835.
• [14] Progressive hearing loss associated with a unique cervical node due to a homozygous SLC29A3 mutation: a very mild phenotype.Eur J Med Genet. 2012 Jan;55(1):56-8. doi: 10.1016/j.ejmg.2011.06.009. Epub 2011 Aug 23.
• [15] Killer cell immunoglobulin-like receptor 2DL4 is expressed in and suppresses the cell growth of Langerhans cell histiocytosis.Oncotarget. 2017 Jun 6;8(23):36964-36972. doi: 10.18632/oncotarget.16936.
• [16] GNA14 Somatic Mutation Causes Congenital and Sporadic Vascular Tumors by MAPK Activation.Am J Hum Genet. 2016 Aug 4;99(2):443-50. doi: 10.1016/j.ajhg.2016.06.010. Epub 2016 Jul 28.
• [17] INSL3 Expression in Leydig Cell Hyperplasia and Leydig Cell Tumors.Appl Immunohistochem Mol Morphol. 2019 Mar;27(3):203-209. doi: 10.1097/PAI.0000000000000567.