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Cancers 2018, 10(6), 169; https://doi.org/10.3390/cancers10060169

The Transition between Telomerase and ALT Mechanisms in Hodgkin Lymphoma and Its Predictive Value in Clinical Outcomes

1
Laboratoire de Radiobiologie et d’Oncologie, IRCM/DSV/CEA, 92265 Fontenay aux Roses, France
2
Cell Environment, DNA Damages R&D, Oncology Section, 75020 Paris, France
3
Institute of Biomedicine, University of Aarhus, DK-8000 Aarhus C, Denmark
4
Department of Radiation Therapy, Gustave Roussy Cancer Campus, 94808 Villejuif, France
5
IRIMAS, Institut de Recherche en Informatique, Mathématiques, Automatique et Signal, Université de Haute-Alsace, 68093 Mulhouse, France
6
MetaSystems GmbH, Robert-Bosch-Str. 6, D-68804 Altlussheim, Germany
7
Université Paris Sud, Service d’hématologie moléculaire et cytogénétique Paul brousse CHU paris Sud, Inserm UMRS935, 94800 Villejuif, France
8
CNRS, Institut Pasteur de Lille, UMR 8161—Immunoregulation of Virus-induced Cancers Team, F-59000 Lille, France
9
CHRU Lille Service des Maladies du Sang, Hopital Huriez, 59000 Lille, France
10
Service de génétique, Groupe hospitalier de la région de Mulhouse Sud-Alsace, 68093 Mulhouse, France
11
Department of Medicine, Gustave Roussy Cancer Campus, 94808 Villejuif, France
*
Author to whom correspondence should be addressed.
Received: 30 March 2018 / Revised: 18 May 2018 / Accepted: 25 May 2018 / Published: 30 May 2018
(This article belongs to the Special Issue Hodgkin's Lymphoma)
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Abstract

Background: We analyzed telomere maintenance mechanisms (TMMs) in lymph node samples from HL patients treated with standard therapy. The TMMs correlated with clinical outcomes of patients. Materials and Methods: Lymph node biopsies obtained from 38 HL patients and 24 patients with lymphadenitis were included in this study. Seven HL cell lines were used as in vitro models. Telomerase activity (TA) was assessed by TRAP assay and verified through hTERT immunofluorescence expression; alternative telomere lengthening (ALT) was also assessed, along with EBV status. Results: Both TA and ALT mechanisms were present in HL lymph nodes. Our findings were reproduced in HL cell lines. The highest levels of TA were expressed in CD30−/CD15− cells. Small cells were identified with ALT and TA. Hodgkin and Reed Sternberg cells contained high levels of PML bodies, but had very low hTERT expression. There was a significant correlation between overall survival (p < 10−3), event-free survival (p < 10−4), and freedom from progression (p < 10−3) and the presence of an ALT profile in lymph nodes of EBV+ patients. Conclusion: The presence of both types of TMMs in HL lymph nodes and in HL cell lines has not previously been reported. TMMs correlate with the treatment outcome of EBV+ HL patients. View Full-Text
Keywords: Hodgkin Lymphoma; telomerase; alternative lengthening of telomeres; EBV Hodgkin Lymphoma; telomerase; alternative lengthening of telomeres; EBV
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M’kacher, R.; Cuceu, C.; Al Jawhari, M.; Morat, L.; Frenzel, M.; Shim, G.; Lenain, A.; Hempel, W.M.; Junker, S.; Girinsky, T.; Colicchio, B.; Dieterlen, A.; Heidingsfelder, L.; Borie, C.; Oudrhiri, N.; Bennaceur-Griscelli, A.; Moralès, O.; Renaud, S.; Van de Wyngaert, Z.; Jeandidier, E.; Delhem, N.; Carde, P. The Transition between Telomerase and ALT Mechanisms in Hodgkin Lymphoma and Its Predictive Value in Clinical Outcomes. Cancers 2018, 10, 169.

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