Retinoic acid receptor alpha (RAR alpha) mutations in human leukemia

The retinoic acid receptor alpha (RAR alpha) plays a central role in the bi ology of the myeloid cellular compartment. Chromosomal translocations invol ving the RAR alpha locus probably represent the malignant initiating events in acute promyelocytic leukemia (APL). Recent studies that identify novel interactions between RAR alpha and the nuclear receptor co-activators and c o-repressors, new functions of the oncogenic RAR alpha fusion proteins and their catabolism in retinoic acid-induced differentiation, and the availabi lity of new transgenic mice models have provided important insights into ou r understanding of the mechanisms by which mutant forms of RAR alpha can be implicated in the development of leukemia. Novel alterations of the RAR al pha gene identified in hematopoietic malignant disorders other than APL, su ch as myelodysplastic syndromes, non-APL acute myeloid leukemias and B-chro nic lymphocytic leukemias, suggest that disruption of the RAR alpha gene mi ght predispose to myeloid and lymphoid disorders.