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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1617-1624.
Prepublished online as a Blood First Edition Paper on November 16, 2007; DOI 10.1182/blood-2007-02-068791.
 Previous Article | Next Article 
Submitted February 2, 2007
Accepted November 3, 2007
Functionally-associated targets in mantle cell lymphoma as
defined by DNA microarrays and RNA interference
Eva Ortega-Paino, Johan Fransson, Sara Ek, and Carl A.K. Borrebaeck*
Department of Immunotechnology, Lund University, Lund, Sweden
* Corresponding author; email: carl.borrebaeck{at}immun.lth.se.
Mantle Cell Lymphoma (MCL) is a non-Hodgkin's lymphoma with poor prognosis. Its hallmark is the translocation t(11:14)q(13;32), leading to overexpression of cyclin D1, a positive regulator of the cell cycle. As Cyclin D1 upregulation is not sufficient for inducing malignant transformation, we combined DNA microarray and RNA interference approaches to identify novel deregulated genes involved in the progression of MCL. DNA microarray analysis identified 46 genes specifically up-regulated in MCL compared to normal B cells and 20 of these were chosen for further studies based on their cellular functions, such as growth and proliferation. The cell line Granta 519 was selected as an MCL in vitro model, to set up the RNAi protocol. To confirm the functionality of overexpression of the 20 disease-associated genes, they were knocked down using siRNAs. In particular, knockdown of three genes, encoding the hepatoma-derived growth factor related protein 3 (HDGFRP3), the frizzled homologue 2 (FZD2), and the dual specificity phosphatase 5 (DUSP5), induced proliferative arrest in Granta 519 MCL cells. These genes emerged as functionally associated in MCL, in relation to growth and survival, and interfering with their function would increase insight into lymphoma growth regulation, potentially leading to novel clinical intervention modalities.
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