MERIT Award Recipient: Pier Paolo Pandolfi, M.D., Ph.D.
PML, PLZF and NPM in the Molecular Pathogenesis of APL
This application focuses on the role of the normal proteins involved in the pathogenesis of APL following the working hypothesis that these genes/proteins may participate in tumorigenesis at large. The focus of this grant is therefore not solely APL per se, but rather how these proteins would participate in tumor suppression and oncogenesis at large. Testing this working hypothesis has been so far rewarding since on the basis of this work the "genes of APL" have by now been firmly implicated in the pathogenesis of other forms of cancer, both solid tumors and hemopoietic malignancies. In addition, through this work we are uncovering how these proteins modulate critical tumor suppressive pathways (e.g. ARF-Mdm2-p53 and PTEN-PI3K-AKT ones), which are universally deregulated in human cancer. In a nutshell, this project tests the provocative hypothesis that functional or physical deregulation/disruption of "leukemia" genes might be extremely relevant to pathogenesis of tumors of diverse histological origins.