The direct Myc target Pim3 cooperates with other Pim kinases in supporting viability of Myc-induced B-cell lymphomas

Linus Plym Forshell 1 , Yongmei Li 1,2,* , Tacha Zi Plym Forshell 1, * , Martina Rudelius 3 , Lisa Nilsson 1 , Ulrich Keller 4 and Jonas Nilsson 1 1 Department of Molecular Biology, Umeå University, Umeå, Sweden 2 Department of Medical Microbiology, Tianjin Medical University, Tianjin, People's Republic of China 3 Department of Pathology, Technical University of Munich, Munich, Germany 4 Department of Medicine, Technical University of Munich, Munich, Germany * Denotes equal contribution Keywords: cancer, lymphoma, oncogenes, c-Myc, Pim-3 Received: June 1, 2011; Accepted: June 2, 2011; Published: June 5, 2011; Correspondence: Jonas Nilsson, e-mail: // // Abstract The Pim kinases are weak oncogenes. However, when co-expressed with a strong oncogene, such as c-Myc, Pim kinases potentiate the oncogenic effect resulting in an acceleration of tumorigenesis. In this study we show that the least studied Pim kinase, Pim-3, is encoded by a gene directly regulated by c-Myc via binding to one of the conserved E-boxes within the Pim3 gene. Accordingly, lymphomas arising in Myc-transgenic mice and Burkitt lymphoma cell lines exhibit elevated levels of Pim-3. Interestingly, inhibition of Pim kinases by a novel pan-Pim kinase inhibitor, Pimi, in Myc-induced lymphoma results in cell death that appears independent of caspases. The data indicate that Pim kinase inhibition could be a viable treatment strategy in certain human lymphomas that rely on Pim-3 kinase expression.