1071P - 3D telomere signatures of Hodgkin-cells at diagnosis identify patients with poor response to conventional chemotherapy

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Lymphomas
Translational Research
Presenter Hans Knecht
Authors H. Knecht1, N. Kongruttanachok2, B. Sawan3, J. Brossard4, S. Prévost5, E. Turcotte5, Z. Lichtensztejn2, D. Lichtensztejn2, S. Mai2
  • 1Haematology, CHUS, J1H 5N4 - Sherbrooke/CA
  • 2Micb, Unversity of Manitoba, R3E0V9 - Winnipeg/CA
  • 3Pathology, CHUS, J1H5N4 - Sherbrooke/CA
  • 4Pediatrics, CHUS, J1H5N4 - Sherbrooke/CA
  • 5Medical Imaging, CHUS, J1H5N4 - Sherbrooke/CA

Abstract

In classical Hodgkin's lymphoma (HL) the malignant mononuclear Hodgkin (H) and multinuclear Reed-Sternberg (RS) cells are characterized by a distinct 3D nuclear telomere organization with shortening of the telomere length and the formation of telomeric aggregates. We asked if the severity of these telomere changes correlates with clinical behaviour of the disease. We evaluated (mainly prospectively) the 3D telomere organization by quantitative fluorescent in situ hybridization (Q-FISH) on diagnostic biopsies from 20 patients who were good responders and compared them with 20 diagnostic biopsies of 11 patients with refractory or relapsing HL (11 initial biopsies, five confirming progressions and four confirming relapses). The H-cells from patients with refractory/relapsing disease contained a significantly higher percentage of very small telomeres (p < 0.05) and telomere aggregates (p < 0.05) compared with H-cells of patients entering rapid remission. In order to eliminate therapy related changes of the 3D nuclear telomere organization we compared (prior to any treatment) 10 initial diagnostic biopsies of refractory/relapsing HL with diagnostic biopsies of 10 patients with ongoing long lasting remission (mean 51 months). Importantly, the differences between both groups were highly significant (p < 0.005) for very small telomeres and for aggregates (p < 0.02). Since both groups were treated with standard ABVD chemotherapy, long lasting remission or progression/relapse are independent of the choice of chemotherapy and have to rely on intrinsic factors of the tumour cells. Thus, H-cells of refractory/relapsing HL are characterized by a specific 3D telomere signature, i.e. abundant very small telomeres. 3D telomere Q-FISH identifies these highly aggressive mononuclear H-cells at the first diagnostic biopsy and thus may offer a novel molecular tool to optimize initial treatment.

Disclosure

All authors have declared no conflicts of interest.