The telomere maintenance system in B-CLL. (A) Telomeric structure maintenance involved numerous proteins, whose precise function still remains largely unknown. We summarize here the actual data in the field. The telomeric double-strand DNA protrudes to form a single-strand overhang. The telomerase complex, in gray, is formed by the catalytic subunit hTERT associated with the template RNA named hTR, and Dyskerin. POT1-TTP1 heterodimer binds to the telomeric overhang and activates the processivity of telomerase.²³  hEST1A²⁴  and Ku70/80 interact with the telomerase, whereas RPA1 binds single-strand DNA. Based on studies in yeast, these 3 components are thought to facilitate the access of telomerase to chromosome ends.²  The shelterin complex, in black, is required to protect telomeres.²  TRF1 inhibits telomerase, whereas POT1 behaves either as an activator or an inhibitor of telomerase activity, depending on its mode of fixation to chromosome ends. These complexes interact with DNA-damage response proteins, as KU70/KU80 and the MRN complex (MRE11-RAD50-NBS1). Among these cofactors, those whose down-regulation is associated with telomere shortening, are depicted as crossed-hatched.²  (B) Quantitative PCR analyses were led on cDNA of peripheral B cells from 42 B-CLL patients and 20 healthy donors. All the box-plots correspond to the β-ACTIN normalized data, except for POT1 (RPL13A) and BCL-2 (RPL19) for which no statistical test can be applied on β-actin-derived data. The corresponding P values are shown in each box. The horizontal lines are medians, the boxes 25th percentiles, and the whiskers 75th percentiles. (C,D) Analyses were carried out on cells from a B-CLL patient and a normal healthy donor, before (Co) and after 48 hours of SAC/IL2 (SAC/IL2) treatment. (C) Q-PCR analysis of hTERT expression is shown (reference gene: β-ACTIN). (D) A trap assay was realized to measure telomerase activity, the gel analysis is shown (different lanes of the same gel are shown) for the different conditions tested and for a positive control (HeLa cells), and quantities of protein per assay are mentioned (mg). (E) Fold expression variation of telomeric proteins observed in B-CLL versus normal B cells. F indicates multiplication factor.