title: Three-dimensional Telomere Signatures of Hodgkin- and Reed-Sternberg Cells at Diagnosis Identify Patients with Poor Response to Conventional Chemotherapy.
abstract: In classic Hodgkin lymphoma (HL) the malignant mononuclear Hodgkin (H) and multinuclear Reed-Sternberg (RS) cells are characterized by a distinct three-dimensional 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 the clinical behavior of the disease. We retrospectively evaluated three-dimensional telomere organization by quantitative fluorescent in situ hybridization (Q-FISH) of diagnostic biopsies from 16 patients who were good responders and compared them with 16 diagnostic biopsies of 10 patients with refractory or relapsing HL (eight initial biopsies, four 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 = .027) and telomere aggregates (P = .032) compared with H cells of patients entering rapid remission. These differences were even more significant (P = .002 and P = .013, respectively) when comparing the eight initial diagnostic biopsies of refractory/relapsing HL with diagnostic biopsies of eight patients with ongoing long-lasting remission (mean of 47 months). This specific three-dimensional telomere Q-FISH signature identifies these highly aggressive mononuclear H cells at the first diagnostic biopsy and thus may offer a new molecular marker to optimize initial treatment.
authors.affiliation: Division d'Hématologie, Département de Médecine, CHUS, Université de Sherbrooke, Québec, Canada.
authors.forename: Hans
authors.initials: H
authors.lastname: Knecht
authors.forename: Narisorn
authors.initials: N
authors.lastname: Kongruttanachok
authors.forename: Bassem
authors.initials: B
authors.lastname: Sawan
authors.forename: Josée
authors.initials: J
authors.lastname: Brossard
authors.forename: Sylvain
authors.initials: S
authors.lastname: Prévost
authors.forename: Eric
authors.initials: E
authors.lastname: Turcotte
authors.forename: Zelda
authors.initials: Z
authors.lastname: Lichtensztejn
authors.forename: Daniel
authors.initials: D
authors.lastname: Lichtensztejn
authors.forename: Sabine
authors.initials: S
authors.lastname: Mai