Oncogene-induced senescence distinguishes indolent from aggressive forms of pulmonary and non-pulmonary Langerhans cell histiocytosis

Marco Chilosi, Fabio Facchetti, Anna Caliò, Alberto Zamò, Matteo Brunelli, Guido Martignoni, Andrea Rossi, Licia Montagna, Paola Piccoli, Alessandra Dubini, Andrea Tironi, Sara Tomassetti, Venerino Poletti, Claudio Doglioni

Research output: Contribution to journalArticle

Abstract

The clonal/neoplastic nature of Langerhans cell histiocytosis (LCH) has recently been demonstrated by a high prevalence of BRAF mutations, including pulmonary LCH (PLCH). We hypothesized that BRAF-induced senescence, as demonstrated in nevi and melanoma, is involved in the pathogenesis of LCH and PLCH. In a series of pulmonary (19 cases) and non-pulmonary LCH (19 cases), including five aggressive cases, we investigated occurrence of the BRAF V600E mutation by molecular analysis and/or immunohistochemistry using a validated antibody (VE1). The expression of cell-senescence markers p16INK4a and p21CIP1/WAF1 was also immunohistochemically investigated. We demonstrated that 6/19 cases of LCH and 12/19 cases of PLCH were VE1 positive, matching with molecular analysis, and in all cases both p16INK4a and p21CIP1/WAF1 were expressed, irrespective of BRAF mutation status. Interestingly, all the aggressive cases did not express p16INK4a, thus suggesting that loss of senescence control could be related to clinical aggressiveness of LCH, as in melanoma.

Original languageEnglish
Pages (from-to)2620-2626
Number of pages7
JournalLeukemia and Lymphoma
Volume55
Issue number11
DOIs
Publication statusPublished - Nov 1 2014

Fingerprint

Non-Langerhans-Cell Histiocytosis
Langerhans Cell Histiocytosis
Oncogenes
Lung
Mutation
Nevi and Melanomas
Cell Aging
Melanoma
Immunohistochemistry
Antibodies

Keywords

  • BRAF mutation
  • P16<sup>INK4a</sup>
  • P21<sup>CIP1/WAF1</sup>
  • PLCH
  • Senescence in LCH

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research
  • Medicine(all)

Cite this

Oncogene-induced senescence distinguishes indolent from aggressive forms of pulmonary and non-pulmonary Langerhans cell histiocytosis. / Chilosi, Marco; Facchetti, Fabio; Caliò, Anna; Zamò, Alberto; Brunelli, Matteo; Martignoni, Guido; Rossi, Andrea; Montagna, Licia; Piccoli, Paola; Dubini, Alessandra; Tironi, Andrea; Tomassetti, Sara; Poletti, Venerino; Doglioni, Claudio.

In: Leukemia and Lymphoma, Vol. 55, No. 11, 01.11.2014, p. 2620-2626.

Research output: Contribution to journalArticle

Chilosi, M, Facchetti, F, Caliò, A, Zamò, A, Brunelli, M, Martignoni, G, Rossi, A, Montagna, L, Piccoli, P, Dubini, A, Tironi, A, Tomassetti, S, Poletti, V & Doglioni, C 2014, 'Oncogene-induced senescence distinguishes indolent from aggressive forms of pulmonary and non-pulmonary Langerhans cell histiocytosis', Leukemia and Lymphoma, vol. 55, no. 11, pp. 2620-2626. https://doi.org/10.3109/10428194.2014.887713
Chilosi, Marco ; Facchetti, Fabio ; Caliò, Anna ; Zamò, Alberto ; Brunelli, Matteo ; Martignoni, Guido ; Rossi, Andrea ; Montagna, Licia ; Piccoli, Paola ; Dubini, Alessandra ; Tironi, Andrea ; Tomassetti, Sara ; Poletti, Venerino ; Doglioni, Claudio. / Oncogene-induced senescence distinguishes indolent from aggressive forms of pulmonary and non-pulmonary Langerhans cell histiocytosis. In: Leukemia and Lymphoma. 2014 ; Vol. 55, No. 11. pp. 2620-2626.
@article{f5d7b88102814d1b83621275bb183c36,
title = "Oncogene-induced senescence distinguishes indolent from aggressive forms of pulmonary and non-pulmonary Langerhans cell histiocytosis",
abstract = "The clonal/neoplastic nature of Langerhans cell histiocytosis (LCH) has recently been demonstrated by a high prevalence of BRAF mutations, including pulmonary LCH (PLCH). We hypothesized that BRAF-induced senescence, as demonstrated in nevi and melanoma, is involved in the pathogenesis of LCH and PLCH. In a series of pulmonary (19 cases) and non-pulmonary LCH (19 cases), including five aggressive cases, we investigated occurrence of the BRAF V600E mutation by molecular analysis and/or immunohistochemistry using a validated antibody (VE1). The expression of cell-senescence markers p16INK4a and p21CIP1/WAF1 was also immunohistochemically investigated. We demonstrated that 6/19 cases of LCH and 12/19 cases of PLCH were VE1 positive, matching with molecular analysis, and in all cases both p16INK4a and p21CIP1/WAF1 were expressed, irrespective of BRAF mutation status. Interestingly, all the aggressive cases did not express p16INK4a, thus suggesting that loss of senescence control could be related to clinical aggressiveness of LCH, as in melanoma.",
keywords = "BRAF mutation, P16<sup>INK4a</sup>, P21<sup>CIP1/WAF1</sup>, PLCH, Senescence in LCH",
author = "Marco Chilosi and Fabio Facchetti and Anna Cali{\`o} and Alberto Zam{\`o} and Matteo Brunelli and Guido Martignoni and Andrea Rossi and Licia Montagna and Paola Piccoli and Alessandra Dubini and Andrea Tironi and Sara Tomassetti and Venerino Poletti and Claudio Doglioni",
year = "2014",
month = "11",
day = "1",
doi = "10.3109/10428194.2014.887713",
language = "English",
volume = "55",
pages = "2620--2626",
journal = "Leukemia and Lymphoma",
issn = "1042-8194",
publisher = "Taylor and Francis Ltd.",
number = "11",

}

TY - JOUR

T1 - Oncogene-induced senescence distinguishes indolent from aggressive forms of pulmonary and non-pulmonary Langerhans cell histiocytosis

AU - Chilosi, Marco

AU - Facchetti, Fabio

AU - Caliò, Anna

AU - Zamò, Alberto

AU - Brunelli, Matteo

AU - Martignoni, Guido

AU - Rossi, Andrea

AU - Montagna, Licia

AU - Piccoli, Paola

AU - Dubini, Alessandra

AU - Tironi, Andrea

AU - Tomassetti, Sara

AU - Poletti, Venerino

AU - Doglioni, Claudio

PY - 2014/11/1

Y1 - 2014/11/1

N2 - The clonal/neoplastic nature of Langerhans cell histiocytosis (LCH) has recently been demonstrated by a high prevalence of BRAF mutations, including pulmonary LCH (PLCH). We hypothesized that BRAF-induced senescence, as demonstrated in nevi and melanoma, is involved in the pathogenesis of LCH and PLCH. In a series of pulmonary (19 cases) and non-pulmonary LCH (19 cases), including five aggressive cases, we investigated occurrence of the BRAF V600E mutation by molecular analysis and/or immunohistochemistry using a validated antibody (VE1). The expression of cell-senescence markers p16INK4a and p21CIP1/WAF1 was also immunohistochemically investigated. We demonstrated that 6/19 cases of LCH and 12/19 cases of PLCH were VE1 positive, matching with molecular analysis, and in all cases both p16INK4a and p21CIP1/WAF1 were expressed, irrespective of BRAF mutation status. Interestingly, all the aggressive cases did not express p16INK4a, thus suggesting that loss of senescence control could be related to clinical aggressiveness of LCH, as in melanoma.

AB - The clonal/neoplastic nature of Langerhans cell histiocytosis (LCH) has recently been demonstrated by a high prevalence of BRAF mutations, including pulmonary LCH (PLCH). We hypothesized that BRAF-induced senescence, as demonstrated in nevi and melanoma, is involved in the pathogenesis of LCH and PLCH. In a series of pulmonary (19 cases) and non-pulmonary LCH (19 cases), including five aggressive cases, we investigated occurrence of the BRAF V600E mutation by molecular analysis and/or immunohistochemistry using a validated antibody (VE1). The expression of cell-senescence markers p16INK4a and p21CIP1/WAF1 was also immunohistochemically investigated. We demonstrated that 6/19 cases of LCH and 12/19 cases of PLCH were VE1 positive, matching with molecular analysis, and in all cases both p16INK4a and p21CIP1/WAF1 were expressed, irrespective of BRAF mutation status. Interestingly, all the aggressive cases did not express p16INK4a, thus suggesting that loss of senescence control could be related to clinical aggressiveness of LCH, as in melanoma.

KW - BRAF mutation

KW - P16<sup>INK4a</sup>

KW - P21<sup>CIP1/WAF1</sup>

KW - PLCH

KW - Senescence in LCH

UR - http://www.scopus.com/inward/record.url?scp=84905657472&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84905657472&partnerID=8YFLogxK

U2 - 10.3109/10428194.2014.887713

DO - 10.3109/10428194.2014.887713

M3 - Article

C2 - 24471909

AN - SCOPUS:84905657472

VL - 55

SP - 2620

EP - 2626

JO - Leukemia and Lymphoma

JF - Leukemia and Lymphoma

SN - 1042-8194

IS - 11

ER -