Telomerase reverse transcriptase (TERT), the catalytic component of
telomerase, may also contribute to
carcinogenesis via telomere-length independent mechanisms. Our previous in vitro and in vivo studies demonstrated that short-term
telomerase inhibition by
BIBR1532 impairs cell proliferation without affecting telomere length. Here, we show that the impaired cell cycle progression following short-term TERT inhibition by
BIBR1532 in in vitro models of B-cell
lymphoproliferative disorders, i.e., Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell lines (LCLs), and B-cell
malignancies, i.e.,
Burkitt's lymphoma (BL) cell lines, is characterized by a significant reduction in NF-κB p65 nuclear levels leading to the downregulation of its target gene MYC. MYC downregulation was associated with increased expression and nuclear localization of P21, thus promoting its cell cycle inhibitory function. Consistently, treatment with
BIBR1532 in wild-type zebrafish embryos significantly decreased Myc and increased p21 expression. The combination of
BIBR1532 with
antineoplastic drugs (
cyclophosphamide or
fludarabine) significantly reduced xenografted cells' proliferation rate compared to monotherapy in the zebrafish xenograft model. Overall, these findings indicate that short-term inhibition of TERT impairs cell growth through the downregulation of MYC via NF-κB signalling and supports the use of TERT inhibitors in combination with
antineoplastic drugs as an efficient anticancer strategy.