In vivo analysis of the molecular genetics of acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is a distinct and paradigmatic subtype of myeloid leukemia associated with reciprocal chromosomal translocations always involving the Retinoic Acid Receptor alpha (RAR alpha) gene on chromosome 17 and variable partner genes (X genes) on different chromosomes. As a consequence of these translocations X-RAR alpha and RAR alpha -X fusion genes are generated. RAR alpha fuses to the PML gene in the vast majority of APL cases, and in a few cases to the PLZF, NPM, NuMA and STAT5b genes respectively. In the last few years, the functions of these aberrant fusion proteins and of the normal gene products involved in these translocations have been extensively characterized in vivo in transgenic and KO animal models. Here we will review the important conclusions, the novel questions and paradoxes that stem from this analysis.