A subset of non-Hodgkin lymphomas are known as anaplastic large cell lymphomas (ALCLs). Many of these lymphomas are characterized by inappropriate constant activation of a protein known as ALK, but the molecular mechanisms by which constantly active ALK causes cells to become cancerous and to survive long-term are not known. Now, in a study appearing online in advance of publication in the December print issue of the Journal of Clinical Investigation, researchers from the University of Turin, Italy, have identified two proteins that are required for ALCL cells to become cancerous and/or to survive long-term. Giorgio Inghirami and colleagues analyzed the genes expressed in ALCL cells before and after blocking the constant activation of ALK, using both an approach known as RNAi and chemical ALK inhibitors. A group of genes controlled by constantly active ALK was identified. Further analysis showed that the pro-survival protein BCL2A1 and the gene regulatory protein CEBPB were required for ALCL cells to become cancerous and/or to survive long-term. This study provides evidence that approaches such as RNAi can be used to identify critical mediators of the cancer process, thereby identifying potential therapeutic targets.

TITLE: Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and BCL2A1 as critical target genes

AUTHOR CONTACT:
Giorgio Inghirami
Roberto Piva



JCI table of contents: November 16, 2006

Contact: Karen Honey
Journal of Clinical Investigation