title: Differences in telomerase expression by the CD1a+ cells in Langerhans cell histiocytosis reflect the diverse clinical presentation of the disease.
abstract: Langerhans cell histiocytosis (LCH) is a disease characterized by an uncontrolled clonal proliferation of Langerhans cells, whose aetiology is still unclear. The clonal nature of LCH could support the hypothesis that it is a neoplastic disease with unlimited growth potential. One requirement for unlimited proliferation is the maintenance of telomere length. In a group of 70 patients, we set out to investigate whether a telomere maintenance mechanism is indeed active in LCH cells. This work showed that LCH cells from all restricted skin LCH lesions (6/6) expressed telomerase as assessed by human telomere reverse transcriptase (hTERT) immunohistochemistry, whereas LCH cells from the majority of the bone lesions analysed did not express hTERT (26/34). Interestingly, in contrast to the solitary bone lesions, LCH cells from lesions of multi-system patients always expressed telomerase (11/11), regardless of the lesional site. In situ telomeric repeat amplification protocol (TRAP) assays performed on different lesional sites showed that this telomerase was active. In addition, the telomere length of LCH cells from a hTERT-positive skin multi-system lesion was long and homogeneous when compared to that in the LCH cells from hTERT-negative bone single-system LCH lesions, which was heterogeneous in length. No evidence for an alternative lengthening of telomeres mechanism was found in hTERT-negative lesions. The difference in telomerase expression and telomere length at the different lesional sites and in biopsies from patients with solitary versus multi-system disease appears to reflect the diverse clinical presentation and course of this disease. The results from this study have important implications for understanding the nature of this disease.
authors: Department of Paediatric Immunology, Haematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors: C E T
authors: CE
authors: da Costa
authors: R M
authors: RM
authors: Egeler
authors: M
authors: M
authors: Hoogeboom
authors: K
authors: K
authors: Szuhai
authors: R G
authors: RG
authors: Forsyth
authors: M
authors: M
authors: Niesters
authors: R R
authors: RR
authors: de Krijger
authors: A
authors: A
authors: Tazi
authors: P C W
authors: PC
authors: Hogendoorn
authors: N E
authors: NE
authors: Annels
mesh_terms: D018949:Antigens, CD1 / Q000276:immunology*; D001842:Bone and Bones / Q000276:immunology / Q000473:pathology; D002648:Child; D015726:Giant Cells / Q000378:metabolism / Q000473:pathology; D006646:Histiocytosis, Langerhans-Cell / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007801:Langerhans Cells / Q000201:enzymology / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D019098:Telomerase / Q000032:analysis*; D016615:Telomere / Q000473:pathology
chemical_list: D018949:Antigens, CD1; C419393:CD1a antigen; C509186:TERT protein, human; D019098:Telomerase