Figure 6.

Increased IGH remodeling in Sm-3’RRrec^High chronic lymphocytic leukemia cells is potentiated by high levels of c-MYC expression. (A) Relative telomere length (RTL) measured by specific quantitative real time polymerase chain reaction relative to the human β globin gene (Sm-3’RRrec^Low, N=33; Sm-3’RRrec^High, N=12; healthy volunteer [HV] peripheral blood mononuclear cells [PBMC], N=6). Telomere length was significantly shorter in the Sm-3’RRrec^High group compared to the Sm-3’RRrec^Low group and HV PBMC. (B) c-MYC expression was higher in Sm-3’RRrec^High (N=6) compared to Sm-3’RRrec^Low chronic lymphocytic leukemia (CLL) samples (N=7). (C) Detection of class switch recombination (CSR) and Sm-3’RR recombination (Sm-3’RRrec) junctions in activated CH12F3 clones overexpressing or not MYC in the presence of activation induced-cytidine deaminase (AID) (CSR: AID⁺, N=1 and AID⁺MYC^tg, N=3; Sm-3’RRrec: AID⁺, N=1 and AID⁺ MYC^tg, N=3) suggested that c-MYC tends to increase CSR and Sm-3’RRrec counts. This was also observed for Sm-3’RRrec in the absence of AID (D), as Sm-3’RRrec junctions, even if rare, were detectable in CH12F3 AID^KO clones (N=2) and appeared to increase with MYC overexpression (AID^KO MYC^tg, N=2). No CSR junctions were detected in the absence of AID (AID^KO, N=1), even with MYC overexpression (AID^KOMYC^tg, N=3). Graphs represent the mean ± standard error of the mean. Statistical analyses were performed using unpaired t test. KO: knockout; tg: transgenic; 3’RR: 3’ regulatory region; NS: not significant; *P<0.05; **P<0.01; ***P<0.001.