Monitorización de la enfermedad mínima residual mediante detección conjunta de los reordenamientos PML/RARα y RARα/PML en la leucemia promielocítica aguda

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Vol. 114. Issue 8.

Pages 281-285 (January 2000)

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Vol. 114. Issue 8.

Pages 281-285 (January 2000)

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DOI: 10.1016/S0025-7753(00)71270-X

Monitorización de la enfermedad mínima residual mediante detección conjunta de los reordenamientos PML/RARα y RARα/PML en la leucemia promielocítica aguda

Monitoring of minimal residual disease by combined detection of PML/RARα and RARα/PML rearrangements in acute promyelocytic leukemia

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Pascual Bolufer,a,

Corresponding author

boluferpas@gva.es

Correspondencia: Dr. P. Bolufer Gilabert. Laboratorio de Biología Molecular (Laboratorio de Hormonas). Centro Maternal. Hospital Universitario La Fe. Avda. Campanar, 21. 46009 Valencia

, Eva Barragána, Miguel Ángel Sanzb, Guillermo Martínb, Enrique Lermaa, Esperanza Afán de Riberaa

a Laboratorio de Biología Molecular. Departamento de Biopatología Clínica

b Sección de Hematología Clínica. Servicio de Hematología y Hemoterapia. Hospital Universitario La Fe. Valencia

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Fundamento

: La ajustada sensibilidad del metodo de RT-PCR empleado en la deteccion del reordenamientoPML/RARα en la leucemia promielocitica aguda (LPA), en comparacion con lamayor sensibilidad alcanzada para otros reordenamientos, justifico que en el presente estudiose planteara la monitorizacion de la enfermedad minima residual (EMR) en la LPA determinandoconjuntamente el reordenamiento RARα y el RARα/PML.

Pacientes Y Métodos

: Se incluyeron 56 pacientes con LPA tratados siguiendo el protocolo PETHEMALPA-96. La deteccion de PML/RARα se efectuo segun el metodo de Biondi et al y la deRARα/PML siguiendo el procedimiento de Grimwade D et al (Human Press Inc.).

Resultados

: RARα/PML se detecto en el 90% (20/22) de los pacientes al diagnostico positivopara PML/RARα. En la postinduccion, RARα/PML se detecto en el 74% de los pacientes(14/19) frente al 37% (7/19) de PML/RARα. Asimismo, en algunas muestras en la posconsolidacion(2/11) se detecto RARα/PML, siendo negativas para PML/RARα. En los pacientes enmantenimiento se detecto una mayor proporcion de positividades (6/28) para RARα/PML quepara PML/RARα (2/28). En un paciente en remision completa, RARα/PML precedio a la apariciondel PML/RARα y persistio un mayor tiempo tras la negativizacion de PML/RARα. En elgrupo de pacientes seguidos desde el diagnostico se observo que RARα/PML suele negativizarseun mes despues de la negativizacion de PML/RARα.

Conclusiones

: RARα/PML se expresa en el 90% de los pacientes con LPA al diagnostico.RARα/PML se detecta en una mayor proporcion de muestras recogidas durante la evolucion quePML/RARα. RARα/PML persiste un mayor tiempo que PML/RARα tras el tratamiento inicial.

Palabras clave:

RARa/PML

PML/RARa

Leucemia promielocítica aguda

Monitorización

Enfermedad mínima residual

Background

: Molecular assay commonly used to detect the PML/RARá rearrangement in acutepromyelocytic leukemia (APL) has the limited sensitivity in comparison with the higher sensitivityof RARá/PML detection. This prompted us to perform both assays in parallel to monitor agroup of APL.

Patients and Methods

: The study included 56 APL patients mainly treated according with thePETHEMA LPA-96 protocol. The PML/RARá was detected according with Biondi's et al methodand the RARá/PML following the Grimwade's et al RT-PCR method (Human Press Inc.).

Results

: RARá/PML rearrangement was detected in 90% (20/22) of the patients at diagnosis positivesfor PML/RARá. RARá/PML was detected in 74%(14/19) of post-induction samples versus37% (7/19) of positives for PML/RARá. Likewise RARá/PML rearrangement was detected in somepost-consolidation samples (2/11) that all were PMI/RARá negatives. In patients in maintenanceregimen a greater proportion of RARá/PML positives (6/28) versus PML/RARá (2/28) were observed.In a patient in complete remission RARá/PML preceded the positivity of PML/RARá and persistedafter PMI/RARá negativization. The results of the patients monitored since the diagnosisshowed that RARá/PML revert to negative one month after PML/RARá negativization.

Conclusions

: RARá/PML rearrangement is not expressed in the totality of the APL patients, butin only a 90% of them. RARá/PML rearrangement was detected in a greater proportion of samplesthan PML/RARá. RARá/PML rearrangement lasted longer than PML/RARá after treatment.