The theory of APL

Acute promyelocytic leukemia (APL) is associated with reciprocal and balanc ed chromosomal translocations always involving the Retinoic Acid Receptor a lpha (RAR alpha) gene on chromosome 17 and variable partner genes (X genes) on distinct chromosomes. RARa fuses to the PML gene in the vast majority o f APL cases, and in a few cases to the PLZF, NPM, NuMA and STAT5b genes. As a consequence, X-RAR alpha and RAR alpha -X fusion genes are generated enc oding aberrant fusion proteins that can interfere with X and/or RAR alpha f unction. Here we will review the relevant conclusions and the open question s that stem from a decade of in giro analysis of APL pathogenesis in the mo use in transgenic and knock-out models.