Chunk #9 — Introduction — MiR-15/16 and DLEU7 at 13q14: a unique collaboration of coding and noncoding genes in indolent CLL — DLEU7, a second tumor suppressor at 13q14
APRIL and its close relative BAFF are recent members of TNF superfamily expressed almost exclusively in lymphoid cells [24]. Interestingly, both BAFF and APRIL show elevated expression levels in various B-cell malignancies including diffuse large cell lymphoma, mantle cell lymphoma and CLL [21, 24]. APRIL binds with high affinity to two receptors, BCMA (B-cell maturation antigen) and TACI, both are members of TNF receptor superfamily (Figure 1) [24]. BCMA is mostly expressed in mature B- and T-cells, while TACI is detected in activated T-cells and subpopulations of B-cells [24]. They stimulate NF-kB pathway by interaction with various TRAFs [24]. Thus, NF-kB activation through TACI and BCMA could be important in the pathogenesis of CLL [21]. Since DLEU7 is located within the 13q14 deleted region we investigated whether its expression has an effect on NF-kB activation by TACI and BCMA. Transfection experiments confirmed our hypothesis: Dleu7 expression inhibited NF-kB activation by BCMA over 5 fold, similarly, NF-kB activation by TACI was inhibited over 4 fold [20]. Thus, we demonstrated that Dleu7 functions as NF-kB inhibitor in a pathway critical for the pathogenesis of CLL (Figure 1).
