Key Features of the Paper
STUDY AIM
To help explain why ATO can induce remission in ATRA-resistance APL Patients, whilst the prognosis in ATO-resistance APL patients are poor.
Methods
This is a report of a case study of a patient with low-risk APL who presented with a history of first relapse after conventional treatments (ATRA plus ATO, four courses of ATO).
Results
The distinctly uncommon clinical course of this patient was associated with a mutation in the PML allele and a novel mutation harbored in the RARA allele simultaneously. These mutations were not detected at initial diagnosis.
Using direct sequencing we studied the PML-RARA fusion transcripts of this patient and found that they are not the same as normal PML and RARA alleles obtained from patients with relapsed APL who have not received conventional chemotherapy previously.
Conclusion
Previous studies have suggested that targeted PML-RARA removal is a fundamental event that enables ATRA-induced APL cell differentiation. PML mutation is identical to the one most commonly encountered in the PML-RARA fusion when resistance to ATO develops. This may explain why the use of ATO can induce remission in ATRA-resistance APL patients, while the prognosis of ATO-resistance APL patients are very poor.