[Monitoring of minimal residual disease with the combined detection of PML/RAR alpha and RAR alpha/PML rearrangements in acute promyelocytic leukemia].
BACKGROUND
Molecular assay commonly used to detect the PML/RAR alpha rearrangement in acute promyelocytic leukemia (APL) has the limited sensitivity in comparison with the higher sensitivity of RAR alpha/PML detection. This prompted us to perform both assays in parallel to monitor a group of APL.


METHODS
The study included 56 APL patients mainly treated according with the PETHEMA LPA-96 protocol. The PML/RAR alpha was detected according with Biondi's et al method and the RAR alpha/PML following the Grimwade's et al RT-PCR method (Human Press Inc.).


RESULTS
RAR alpha/PML rearrangement was detected in 90% (20/22) of the patients at diagnosis positives for PML/RAR alpha. RAR alpha/PML was detected in 74% (14/19) of post-induction samples versus 37% (7/19) of positives for PML/RAR alpha. Likewise RAR alpha/PML rearrangement was detected in some post-consolidation samples (2/11) that all were PMI/RAR alpha negatives. In patients in maintenance regimen a greater proportion of RAR alpha/PML positives (6/28) versus PML/RAR alpha (2/28) were observed. In a patient in complete remission RAR alpha/PML preceded the positivity of PML/RAR alpha and persisted after PMI/RAR alpha negativization. The results of the patients monitored since the diagnosis showed that RAR alpha/PML revert to negative one month after PML/RAR alpha negativization.


CONCLUSIONS
RAR alpha/PML rearrangement is not expressed in the totality of the APL patients, but in only a 90% of them. RAR alpha/PML rearrangement was detected in a greater proportion of samples than PML/RAR alpha. RAR alpha/PML rearrangement lasted longer than PML/RAR alpha after treatment.
Bolufer
P
P
Departamento de Biopatología Clínica, Hospital Universitario La Fe, Valencia. boluferpas@gva.es
Barragán
E
E
Sanz
M A
MA
Martín
G
G
Lerma
E
E
Afán de Ribera
E
E
D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D012680:Sensitivity and Specificity
D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein