Molecular genetics of acute promyelocytic leukemia

The remarkable success of retinoic acid in the treatment of acute promyeloc ytic leukemias and the subsequent discovery that mutant forms of a retinoid acid receptor (RAR alpha) are invariably associated with this disease has generated considerable interest among both clinicians and basic scientists. Studies both in cell culture and in transgenic animals suggest that mutant RARs interfere with normal retinoid-mediated transactivation and granulocy tic differentiation, More recently, a pivotal link between transcriptional silencing, the oncogenic functions of RAR mutants, and hormonal responses i n APL patients has been established. These studies have greatly advanced ou r understanding of the molecular changes Involved in leukemogenesis, have h elped to reveal new aspects of cellular differentiation, and might read to improved treatment strategies for human leukemias.