@article{Shahab Uddin_Azhar R Hussain_Maqbool Ahmed_Khawar Siddiqui_Fouad Al-Dayel_Prashant Bavi_Khawla S. Al-Kuraya_2012, place={Pavia, Italy}, title={Overexpression of FoxM1 offers a promising therapeutic target in diffuse large B-cell lymphoma}, volume={97}, url={https://haematologica.org/article/view/6355}, DOI={10.3324/haematol.2011.053421}, abstractNote={<strong>Background</strong> FoxM1 has been shown to play a critical role in the pathogenesis of various epithelial malignancies. However, its role in lymphoid malignancies has not been fully clarified. We, therefore, investigated the role of FoxM1 expression in a large cohort of diffuse large B-cell lymphoma samples and panel of cell lines.<strong>Design and Methods</strong> FoxM1 expression was investigated in a large series of diffuse large B-cell lymphoma tissues in a tissue microarray format by immunohistochemistry. Apoptosis was measured by flow cytometry and protein expression was detected by immunoblotting using diffuse large B-cell lymphoma cell lines following treatment with either pharmacological inhibitor of FoxM1 or small interference RNA knockdown strategy. Invasion/migration and soft agar colony assays were also performed following treatment with FoxM1 inhibitor.<strong>Results</strong> FoxM1 expression was detected in 84.6% of diffuse large B-cell lymphoma tumors and found to be significantly associated with proliferative tumor marker Ki67 (<em>P</em><0.0001), matrix metalloproteinases-2 (<em>P</em>=0.0008), matrix metalloproteinases-9 (<em>P</em>=0.0002), S-phase kinase associated protein-2 (<em>P</em><0.0001) and inversely associated with p27 expression (<em>P</em>=0.0215). Expression of small interference RNA targeted against FoxM1 or treatment of diffuse large B-cell lymphoma cells with thiostrepton caused its downregulation accompanied by decreased expression of matrix metalloproteinases-2 and matrix metalloproteinases-9. Inhibition of FoxM1 in diffuse large B-cell lymphoma cells also decreased invasive and migratory capability, and induced caspase dependent apoptosis via activation of the mitochondrial apoptotic pathway. Finally, combined thiostrepton and bortezomib at sub-toxic doses led to efficient apoptosis in diffuse large B-cell lymphoma cells.<strong>Conclusions</strong&gt; Altogether, these results suggest that FoxM1 is over-expressed in the majority of diffuse large B-cell lymphoma samples. These data also indicate that targeting FoxM1 signaling can serve as a potential therapeutic modality in the management of diffuse large B-cell lymphoma.}, number={7}, journal={Haematologica}, author={Shahab Uddin and Azhar R Hussain and Maqbool Ahmed and Khawar Siddiqui and Fouad Al-Dayel and Prashant Bavi and Khawla S. Al-Kuraya}, year={2012}, month={Jul.}, pages={1092-1100} }