Telomere length shortening in Langerhans cell histiocytosis

Bechan, Gitanjali I.; Meeker, Alan K.; Marzo, Angelo M. De; Racke, Frederick; Jaffe, Ronald; Sugar, Elizabeth A.; Arceci, Robert J.

doi:10.1111/j.1365-2141.2007.06904.x

Cited by 21 publications

(10 citation statements)

References 33 publications

(46 reference statements)

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“…In contrast to our results, a recent study from Bechan et al. (65), using quantitative immune fluorescence, showed that LCH cells display significant telomere shortening in all clinical phenotypes of LCH studied. This discrepancy may reflect the differences in sensitivity of the techniques used to assess the telomere length of the cells.…”

Section: Are Lch Cells Intrinsically Aberrant?contrasting

confidence: 99%

Langerhans cell histiocytosis: fascinating dynamics of the dendritic cell–macrophage lineage

Egeler

Halteren

Hogendoorn

et al. 2010

Immunological Reviews

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In its rare occurrence, Langerhans cell histiocytosis (LCH) is a dangerous but intriguing deviation of mononuclear phagocytes, especially dendritic cells (DCs). Clinically, the disease ranges from self-resolving or well manageable to severe and even fatal. LCH lesions in skin, bone, and other sites contain high numbers of cells with phenotypic features resembling LCs admixed with macrophages, T cells, eosinophils, and multinucleated giant cells. Here we review current progress in the LCH field based on two central questions: (i) are LCH cells intrinsically aberrant, and (ii) how does the lesion drive pathogenesis? We argue that LCH cells may originate from different sources, including epidermal LCs, tissue Langerin(+) DCs, or mononuclear phagocyte precursors. Current and prospective in vitro and in vivo models are discussed. Finally, we discuss recent insights into plasticity of T-helper cell subsets in light of the lesion microenvironment. LCH continues to provide urgent clinical questions thereby inspiring innovative DC lineage research.

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Section: Are Lch Cells Intrinsically Aberrant?contrasting

confidence: 99%

Langerhans cell histiocytosis: fascinating dynamics of the dendritic cell–macrophage lineage

Egeler

Halteren

Hogendoorn

et al. 2010

Immunological Reviews

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“…However, according to a recent report there is no evidence for telomere lengthening in LCH in any stages of the disease (Bechan et al, 2007). Nevertheless, as for TP53, there seems to be no genetic basis for the observed telomerase upregulation.…”

Section: Discussionmentioning

confidence: 88%

No genomic aberrations in Langerhans cell histiocytosis as assessed by diverse molecular technologies

Costa

Szuhai

Eijk

et al. 2008

Genes Chromosomes & Cancer

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The etiology of Langerhans cell histiocytosis (LCH), a disease characterized by uncontrolled proliferation of Langerhans cells, is unknown. Although some believe that LCH is reactive, others support a neoplastic origin. We tested the hypothesis that LCH is neoplastic by investigating potential consistent chromosomal aberrations in LCH cells. We used multiparameter DNA flow cytometry to analyze the DNA ploidy LCH cells in 20 cases, performed karyotype analysis in 31 cases, array-based comparative genomic hybridization (arrayCGH) and single nucleotide polymorphism (SNP) arrays with DNA from flow-sorted CD1a-positive and CD1a-negative cells in 19 cases. Ploidy analysis revealed diploid DNA content in all cases. The karyotype of all patients analyzed was normal, excluding the presence of balanced translocations. ArrayCGH and SNP arrays did not show genome abnormalities. Despite positive TP53 protein immunohistochemical staining, sequencing of exon 5 to 8 of p53 gene showed no alterations in 7 cases. This study strongly suggests that gross chromosomal abnormalities do not cause LCH. Although we cannot exclude cryptic point mutations in as yet unidentified genes, this study of 72 LCH cases shows that LCH may be the result of restricted oligoclonal stimulation rather than unlimited neoplastic proliferation. (c) 2008 Wiley-Liss, Inc.

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“…BCL2L1 (48,49), CASP3 (48), CASP8 (50), CCL2 (10), CCL20/MIP-3α (51), CD44 (52), CCL22 (10,53,54), CCR6 (51), CCR7 (55), CD11b/ITGAM (25,52,56–58), CD11c/ITGAX (25,38,52,57), CD14 (39), CD1a (Reviewed in 3,4,10), CD2 (25,52,58,59), CD36 (60), CD40 (39,61), CD49d/ITGA4 (25), CD54/ICAM1 (25,52), CD58 (25,52), CD68 (57), CD80 (39), CD83 (39,62), CD86 (39), cdc2a/p16 (49), CD-SIGN/CD209 (63), CFLAR (50), CLA/SELPLG (64), c-myc (65), CXCL11/I-TAC (51), CXCL8/IL-8 (10), DC-LAMP/CD208 (39), E-cadherin/CDH1 (25,26), FADD (50), FAS (66), Fascin/FSCN1 (67,68), FASLG (66), FLT3LG (38), GMCSF/CSF2 (10,69,70), GM-CSFR/CSF2RA (70), H-ras (65), hTERT (71,72), IFNγ (10,23,24), IL-10 (10,32,39), IL-17A (22), IL1R1 (73), IL-1α (10,23,24), IL-1β (10,23,24), IL-2 (10,24), IL-22 (22), IL2Rα/CD25 (58,74,75), IL-3 (10,24), IL-4 (10,23,24), IL-6 (10), Ki67 (…”

Section: Figurementioning

confidence: 99%

Cell-Specific Gene Expression in Langerhans Cell Histiocytosis Lesions Reveals a Distinct Profile Compared with Epidermal Langerhans Cells

Allen

Peters³

et al. 2010

The Journal of Immunology

269

272

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Langerhans-cell histiocytosis (LCH) is a rare disease characterized by heterogeneous lesions containing CD207+ Langerhans cells and lymphocytes that can arise in almost any tissue and cause significant morbidity and mortality. After decades of research, the cause of LCH remains speculative. A prevailing model suggests that LCH arises from malignant transformation and metastasis of epidermal Langerhans cells. In this study, CD207+ cells and CD3+ T cells were isolated from LCH lesions to determine cell-specific gene expression. Compared to control epidermal CD207+ cells, the LCH CD207+ cells yielded 2113 differentially-expressed genes (FDR<0.01). Surprisingly, expression of many genes previously associated with LCH, including cell-cycle regulators, pro-inflammatory cytokines and chemokines were not significantly different from control LCs in our study. However, several novel genes whose products activate and recruit T cells to sites of inflammation, including SPP1 (osteopontin), were highly over-expressed in LCH CD207+ cells. Furthermore, several genes associated with immature myeloid dendritic cells were over-expressed in LCH CD207+ cells. Compared to the peripheral CD3+ cells from LCH patients, the LCH lesion CD3+ cells yielded only 162 differentially-regulated genes (FDR<0.01), and the expression profile of the LCH lesion CD3+ cells was consistent with an activated regulatory T cell phenotype with increased expression of FOXP3, CTLA4 as well as SPP1. Results from this study support a model of LCH pathogenesis in which lesions do not arise from epidermal Langerhans cells, but from accumulation of bone-marrow derived immature myeloid dendritic cells that recruit activated lymphocytes.

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Telomere length shortening in Langerhans cell histiocytosis

Cited by 21 publications

References 33 publications

Langerhans cell histiocytosis: fascinating dynamics of the dendritic cell–macrophage lineage

Langerhans cell histiocytosis: fascinating dynamics of the dendritic cell–macrophage lineage

No genomic aberrations in Langerhans cell histiocytosis as assessed by diverse molecular technologies

Cell-Specific Gene Expression in Langerhans Cell Histiocytosis Lesions Reveals a Distinct Profile Compared with Epidermal Langerhans Cells

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