Anaplastic Large Cell Lymphoma (ALCL) is a non-Hodgkin lymphoma of children and young adults with poor survival rates. ALCLs often occur with a chromosomal translocation that results in expression of the NPM-ALK oncoprotein. The molecular mechanism of NPM-ALK resulting in lymphoma growth are not fully understood. In a murine NPM-ALK lymphoma-model with T-cell specific deletion of cJun and JunB we could drastically delay lymphoma development and metastases. We identified PDGFRB as a direct transcriptional target of cJun and JunB. Blockage of the PDGFRβ activity significantly prolonged survival of NPM-ALK transgenic mice and severely reduced the growth of xenografted NPM-ALK tumors. In addition, we demonstrate that PDGFRβ is upregulated in human ALCL tumor specimens. Inhibition of the PDGFRβ in a terminal stage patient with NPM-ALK expressing ALCL which was refractory to any conventional therapy resulted in full remission within 10 days of treatment. We herwith certify the PDGFRB as a novel cJun/JunB target essential for ALCL development. Our data for the first time unravel a highly effective targeted therapy with the outlook to make ALCL a curable disease.
Off Label Use: Imatinib for treatment of ALCL.
Asterisk with author names denotes non-ASH members.