Positive evidence for a role of the PML pathway in leukemogenesis of acute promyelocytic leukemia

Acute Promyelocytic Leukemia is characterized by the production of oncogenic Retinoic acid receptor alpha (RARα) fusion proteins. The most frequently observed fusion protein is PML-RAR (PR). All fusion partners of RARα contribute an oligomerization motif. Previously, we have shown that replacement of PML with an unrelated oligomerization domain renders RARα oncogenic, albeit also reduces its potency. Here we have, conversely, attempted to create a more oncogenic RARα fusion protein. To do so, we fused the corresponding PML domain of murine PML to RARα. As PML, different from RARα, is only moderately conserved be…