Acute promyelocytic leukemia (APL) is a subtype of acute myelogenous leukemia (AML) that arises due to a block in blood cell development at the promyelocytic stage of differentiation. APL is characterized by a t(15;17) chromosomal translocation that fuses the gene encoding promyelocytic leukemia protein (PML) to that encoding retinoic acid receptor alpha (RARA). The product of this genetic aberration, the PML/RARA fusion protein, is an oncoprotein and represents one of the major contributing factors for APL development.
Research during the past 20 years have led to the discovery of two reagents, al trans retinoic acid (ATRA) and arsenic trioxide (ATO), that cure APL through a mechanism that involves direct targeting of the PML/RARA oncoprotein. Since APL is caused by a defined genetic alteration (the t(15;17) translocation) and because of the success of treating this disease by targeted therapeutic drugs, APL has become one of the most attractive model diseases for the development of targeted cancer therapy.
In our work we attempt to elucidate the molecular mechanisms involved in development and treatment of APL. Our goal is to identify therapeutic concepts that can be generalized and applied for treatment of other cancers. To achieve this we use a wide range of molecular biology and cell biology techniques, including live cell imaging, mass spectrometry and flow cytometry. We also use mouse models for in vivo experiments and we collaborate with clinicians to study primary tumor samples.
|PML bodies||click to enlarge image