The BCL-2 family protein inhibitor ABT-737 as an additional tool for the treatment of EBV-associated post-transplant lymphoproliferative disorders.

ABSTRACT: Post-transplant lymphoproliferative disorders (PTLD) and Burkitt's lymphoma (BL) are B-cell malignancies strongly associated with Epstein-Barr virus (EBV) infection. In these lymphoproliferative disorders, EBV infection induces an increase in the expression of the anti-apoptotic protein BCL-2. Given its chemoprotective effect, BCL-2 constitutes an attractive target for new therapeutic strategies for EBV-positive B-cell malignancies. Here, we show that ABT-737, a small inhibitor of BCL-2, BCL-X(L), and BCL-w, strongly induced apoptosis in vitro in EBV-positive lymphoblastoid cell lines (which is a model for PTLD), whereas BL was less sensitive. ABT-737 reduced tumor growth and increased the overall survival of mice in a xenograft model of PTLD but had no effect on BL xenograft mice. ABT-737

SUBMITTER: Robert A 

PROVIDER: S-EPMC7530790 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature