NEWS
2010 - 05 - 10 Laboratory of Experimental Hemato-Oncology
The work of Victoria El-Khoury from the Laboratory of Experimental Hemato-Oncology has been recently published in the journal "Molecular Cancer Therapeutics". This study describes the death pathways activated by the isotype-selective histone deacetylase (HDAC) inhibitor MGCD0103 in B-cell chronic lymphocytic leukemia cells from 32 patients.
Several data support the use of histone deacetylase (HDAC) inhibitors as single anticancer agents or in combination chemotherapy. The activity of MGCD0103 has been demonstrated in hematological malignancies, but the molecular basis behind its cytotoxicity is still poorly understood.This study provides evidence that chronic lymphocytic leukemia cells are more sensitive than normal cells to MGCD0103, and that this HDAC inhibitor kills CLL cells by activating the intrinsic pathway of apoptosis and triggering a mitochondrial death amplification loop in ex vivo. These findings are relevant to understand and overcome MGCD0103 resistance mechanisms and consider its use in combination regimens.
Reference:
Victoria El-Khoury, Etienne Moussay, Bassam Janji, Valérie Palissot, Nasséra Aouali, Nicolaas H.C. Brons, Kris Van Moer, Sandrine Pierson, Eric Van Dyck, and Guy Berchem.
The Histone Deacetylase Inhibitor MGCD0103 Induces Apoptosis in B-Cell Chronic Lymphocytic Leukemia Cells through a Mitochondria-Mediated Caspase Activation Cascade. Mol Cancer Ther; Published OnlineFirst April 20, 2010.
http://www.ncbi.nlm.nih.gov/pubmed/20406947