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Telomerase activity in reactive and neoplastic lymphoid tissues: infrequent detection of activity in Hodgkin's
P Brousset1, T al Saati, N Chaouche
1Laboratoire du Groupe d'Etude des Lymphomes Malins (CNRS, CIGH), Toulouse, France.
Insights
Telomerase activity is present in most lymphoid cancers, including non-Hodgkin's lymphoma (NHL). However, it also appears in reactive conditions, suggesting telomerase activity alone cannot distinguish cancer from immune responses.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Telomerase is crucial for cell immortalization and is often active in cancers.
- Its role in lymphoid proliferations, both malignant and reactive, requires further investigation.
Purpose of the Study:
- To assess telomerase activity in various lymphoid tissues and malignancies using the telomeric repeat amplification protocol (TRAP) assay.
- To determine if telomerase activity can differentiate between malignant lymphoid conditions and reactive states.
Main Methods:
- Utilized the sensitive and rapid telomeric repeat amplification protocol (TRAP) assay.
- Analyzed telomerase activity in lymphoblastoid cell lines, lymphoma cell lines, hyperplastic lymph nodes, tonsils, non-Hodgkin's lymphoma (NHL), and Hodgkin's disease (HD) tissues.
Main Results:
- Telomerase activity was detected in all lymphoblastoid and lymphoma cell lines, and 80% of NHL cases.
- Unexpectedly, all hyperplastic lymph nodes and tonsils showed telomerase activity.
- Only 7% of Hodgkin's disease (HD) cases exhibited telomerase activity, with many other cases being uninterpretable or showing low levels.
Conclusions:
- Telomerase activity is not a definitive marker for distinguishing malignant lymphoid proliferations from reactive conditions.
- Hodgkin's disease (HD) appears to be largely telomerase-independent or has transient/low telomerase activity.
- Further microdissection studies are needed to pinpoint cells with telomerase activity in reactive and neoplastic lymphoid tissues.
Abstract:
We used the recently described sensitive and rapid detection assay called telomeric repeat amplification protocol (TRAP) to detect telomerase activity in lymphoblastoid (n = 5) and lymphoma cell lines (n = 7), hyperplastic lymph nodes (n = 6) and tonsils (n = 5), and tissues involved by non-Hodgkin's lymphoma (NHL) (n = 43) and Hodgkin's disease (HD) (n = 14). Clearly evident telomerase activity was found in all lymphoblastoid and lymphoma cell lines, and in 34 of 43 cases (80%) of NHL. These results were expected because of the proliferative and immortal nature of the cell lines and most malignant cells. However, positive results were obtained with the TRAP assay in all hyperplastic lymph nodes and tonsils, which raises the issue of derepression of telomerase activity during an immune response. Telomerase activity alone therefore does not distinguish malignant lymphoid proliferations from reactive states. Telomerase activity was detected in only 1 of 14 cases (7%) of lymphoid tissues involved by HD. Eight of the 13 negative cases were considered to be interpretable because of the lack (3 of 13 cases) or low level (5 of 13 cases) of telomerase inhibition. The five remaining cases could not be evaluated because of their telomerase inhibitor content. The findings imply either transient or very low levels of telomerase activity in HD or that HD for the greater part is a telomerase-independent neoplasm. Microdissection studies are needed to identify subsets of cells carrying telomerase activity in both reactive and neoplastic lymphoid tissues.