A histone deacetylase inhibitor, azelaic bishydroxamic acid, shows cytotoxicity on Epstein-Barr virus transformed B-cell lines: a potential therapy for posttransplant lymphoproliferative disease.
BACKGROUND
Posttransplant lymphoproliferative disease (PTLD), driven by the presence of Epstein-Barr virus (EBV), is becoming an increasingly important clinical problem after solid organ transplantation. The use of immunosuppressive therapy leads to the inhibition of the cytotoxic T cells that normally control the EBV latently infected B cells. The prognosis for many patients with PTLD is poor, and the optimal treatment strategy is not well defined.


METHODS
This study investigates the use of a histone deacetylase inhibitor, azelaic bishydroxamic acid (ABHA), for its ability to effectively kill EBV-transformed lymphoblastoid cell lines.


RESULTS
In vitro treatment of lymphoblastoid cell lines with ABHA showed that they were effectively killed by low doses of the drug (ID50 2-5 microg/ml) within 48 hr. As well as being effective against polyclonal B-cell lines, ABHA was also shown to be toxic to seven of eight clonal Burkitt's lymphoma cell lines, indicating that the drug may also be useful in the treatment of late-occurring clonal PTLD. In addition, ABHA treatment did not induce EBV replication or affect EBV latent gene expression.


CONCLUSIONS
These studies suggest that ABHA effectively kills both polyclonal and clonal B-cell lines and has potential in the treatment of PTLD.
Sculley
Tom B
TB
Queensland Institute of Medical Research and University of Queensland Joint Oncology Program, Herston 4029, Brisbane, Australia.
Buck
Marion
M
Gabrielli
Brian
B
Parsons
Peter G
PG
Krauer
Kenia G
KG
D001402:B-Lymphocytes / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002472:Cell Transformation, Viral; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D016195:G2 Phase / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D008232:Lymphoproliferative Disorders / Q000188:drug therapy*; D008938:Mitosis / Q000187:drug effects; D016377:Organ Transplantation / Q000009:adverse effects*; D014779:Virus Replication / Q000187:drug effects
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C107648:azelaic bishydroxamic acid