THE PML RAR-ALPHA FUSION GENE IN THE DIAGNOSIS AND MONITORING OF ACUTE PROMYELOCYTIC LEUKEMIA/

The acute promyelocytic leukemia (APL)-specific t(15;17) chromosome ab normality is characterized at the molecular level by rearrangement of the PML and RAR alpha( genes, resulting in fusion PML/RAR alpha mRNA a nd a chimeric protein. Besides its relevance in the pathogenesis of th e disease, this hybrid gene represents a specific tumor marker that is rapidly detectable by reverse transcriptase-polymerase chain reaction (RT-PCR) in the RNA extracted from leukemic blasts. Several studies h ave highlighted the clinical relevance of PML/RAR alpha detection, whi ch provides a specific diagnosis, prognostic information, and predicti on of relapse when monitoring residual disease during the follow-up. I n fact, this hybrid gene is detected in 100% of APLs. Rare cases of pa tients with a morphological diagnosis of FAB M3 AML who lack the speci fic PML/RAR alpha abnormality have been reported as being unresponsive to differentiation treatment. Finally, all the studies reported so fa r on PCR monitoring in APL have documented that the identification of small amounts of residual disease at remission strongly predicts impen ding relapse. Thus, RT-PCR of the hybrid PML/RAR alpha gene is current ly performed prospectively as part of cooperative clinical trials aime d at better addressing post-remission treatment in APL.