Epstein-Barr virus (EBV) is a human herpesvirus, which is causally associated with the development of several B lymphocytic malignancies that include Burkitt's lymphomas, Hodgkin's disease, AIDS and posttransplant associated lymphomas. The transforming activity of EBV is orchestrated by several latent viral proteins that mimic and modulate cellular growth promoting and antiapoptotic signaling pathways, which involve among others the activity of protein kinases. In an effort to identify small molecule inhibitors of the growth of EBV-transformed B lymphocytes a library of 254 kinase inhibitors was screened. This effort identified two tyrosine kinase inhibitors and two MEK inhibitors that compromised preferentially the viability of EBV-infected human B lymphocytes. Our findings highlight the possible dependence of EBV-infected B lymphocytes on specific kinase-regulated pathways underlining the potential for the development of small molecule-based therapeutics that could target selectively EBV-associated human B lymphocyte malignancies.
Bibliographical noteFunding Information:
This work was supported by the Greek State Scholarship Foundation (VM), the Sixth Research Framework Programme of the European Union, Project INCA (LSHC-CT-2005-018704) and a Leukemia and Lymphoma Society of America Scholarship (GM). The authors thank the Bodossaki Foundation for providing financial support to acquire imaging equipment, Drs Evangelia Yannaki and Achilles Anagnostopoulos (George Papanicolaou Hospital, Thessaloniki) for valuable advice and assistance with the analysis of human samples and Drs John Kourtzelis and Eudoxia Hatzivassiliou (Aristotle University of Thessaloniki) for critically reading the manuscript.