Analysis oft he oncogenic properties of PML-RARa in Acute Promyelocytic Leukemia

Acute Promyelocytic Leukemia (APL) is characterized by chromosomal translocations. 98% of APL cases carry a t(15;17) translocation, leading to a PML-RARα (hPR) fusionprotein. Due to the high sequence diversity of human and murine PML, we substituted the human PML with its murine counterpart to create a mPML-hRARa (mPR) chimeric protein. mPR is a more potent oncogene in mice than hPR and, different from hPR, also immortalizes primary murine bone marrow. We inactivated the functional domains of mPR to study their impact on leukemogenesis. The disruption of the PML nuclear bodies (PML NBs) is historically an import…