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Type of publication: Baccalaureate Thesis
Type of document:

Year: 2010

Authors: Grießhammer, Isabel

Title: DNA methylation analysis in anaplastic large cell lymphoma (ALCL).

Source: Bakkalaureatsarbeit, Vet. Med. Univ. Wien, pp. 34.


Advisor(s):

Steinborn Ralf

Reviewer(s):
Karaghiosoff Marina

Vetmed Research Units:
VetCore


Abstract:
Every year 12.4 per 100.000 people in Europe and the United States are diagnosed with Non-Hodgkin-Lymphoma (NHL), whereas the numbers increased over the last decades about 5-10% every year. ALCL represent only 2% of all NHL diagnoses (MAMOT C, 2006). Generally, patients with ALCL respond very sensitive to prevalent chemotherapy, however patients with NPM-ALK fusion protein have a better prospect to be cured than patients suffering from a NPM-ALK negative ALCL. Due to the infrequence of this kind of neoplasm science is still lacking both data and big studies under random conditions. For this reason ALCL needs to be better analysed to gain further knowledge that might lead to new and/ or improved therapies and better chances of cure for the patients. The aim of this research project was to examine whether, similar to other tumors, there can be found changes in epigenetic patterns that provide starting points for a future epigenetic therapy in ALCL. For this reason different ALCL cell lines (KARPAS-299, SR-786, SUDHL-1, MAC-2A) were analysed in terms of hypermethylation of already known “cancer genes” (ESTELLERM et al. 2007, JOHNSTONER W et al. 2002, CHUNGW et al. 2008) and compared to control cells. Further, the protein level of DNMT1 in cancer cells compared to normal cells was analysed. Three of four cell lines (KARPAS-299, SR-786, MAC-2A) show a higher amount of DNMT1 than normal T cells while there was no detectable amount of DNMT1 in one of four cell lines (SUDHL-1) as well as in the control cells. The results of these two experiments implied the analysis of the effect of the DNMT inhibitor 5-aza-2’- deoxycytidine on the growth of tumor cells. A dose dependent decrease of cell population doublings after 5-aza-CdR treatment was found. The findings of the study indicate an aberrant methylation pattern in ALCL cell lines and confirm their sensitivity to 5-aza-CdR which is essential for further in vivo and clinical studies.

Keywords:
ALCL, anaplastic large cell lymphoma, NPM-ALK, DNA methylation, DNMT inhibitor, 5-aza-CDR


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