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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
Pascual Bolufer,a,
Autor para correspondencia
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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        "resumen" => "<span class="elsevierStyleSectionTitle">Fundamento</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#58; La ajustada sensibilidad del metodo de RT-PCR empleado en la deteccion del reordenamientoPML&#47;RAR&#945; en la leucemia promielocitica aguda &#40;LPA&#41;&#44; en comparacion con lamayor sensibilidad alcanzada para otros reordenamientos&#44; justifico que en el presente estudiose planteara la monitorizacion de la enfermedad minima residual &#40;EMR&#41; en la LPA determinandoconjuntamente el reordenamiento RAR&#945; y el RAR&#945;&#47;PML&#46;</p> <span class="elsevierStyleSectionTitle">Pacientes Y M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">&#58; Se incluyeron 56 pacientes con LPA tratados siguiendo el protocolo PETHEMALPA-96&#46; La deteccion de PML&#47;RAR&#945; se efectuo segun el metodo de Biondi et al y la deRAR&#945;&#47;PML siguiendo el procedimiento de Grimwade D et al &#40;Human Press Inc&#46;&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">&#58; RAR&#945;&#47;PML se detecto en el 90&#37; &#40;20&#47;22&#41; de los pacientes al diagnostico positivopara PML&#47;RAR&#945;&#46; En la postinduccion&#44; RAR&#945;&#47;PML se detecto en el 74&#37; de los pacientes&#40;14&#47;19&#41; frente al 37&#37; &#40;7&#47;19&#41; de PML&#47;RAR&#945;&#46; Asimismo&#44; en algunas muestras en la posconsolidacion&#40;2&#47;11&#41; se detecto RAR&#945;&#47;PML&#44; siendo negativas para PML&#47;RAR&#945;&#46; En los pacientes enmantenimiento se detecto una mayor proporcion de positividades &#40;6&#47;28&#41; para RAR&#945;&#47;PML quepara PML&#47;RAR&#945; &#40;2&#47;28&#41;&#46; En un paciente en remision completa&#44; RAR&#945;&#47;PML precedio a la apariciondel PML&#47;RAR&#945; y persistio un mayor tiempo tras la negativizacion de PML&#47;RAR&#945;&#46; En elgrupo de pacientes seguidos desde el diagnostico se observo que RAR&#945;&#47;PML suele negativizarseun mes despues de la negativizacion de PML&#47;RAR&#945;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">&#58; RAR&#945;&#47;PML se expresa en el 90&#37; de los pacientes con LPA al diagnostico&#46;RAR&#945;&#47;PML se detecta en una mayor proporcion de muestras recogidas durante la evolucion quePML&#47;RAR&#945;&#46; RAR&#945;&#47;PML persiste un mayor tiempo que PML&#47;RAR&#945; tras el tratamiento inicial&#46;</p>"
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        "resumen" => "<span class="elsevierStyleSectionTitle">Background</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">&#58; Molecular assay commonly used to detect the PML&#47;RAR&#225; rearrangement in acutepromyelocytic leukemia &#40;APL&#41; has the limited sensitivity in comparison with the higher sensitivityof RAR&#225;&#47;PML detection&#46; This prompted us to perform both assays in parallel to monitor agroup of APL&#46;</p> <span class="elsevierStyleSectionTitle">Patients and Methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">&#58; The study included 56 APL patients mainly treated according with thePETHEMA LPA-96 protocol&#46; The PML&#47;RAR&#225; was detected according with Biondi&#39;s et al methodand the RAR&#225;&#47;PML following the Grimwade&#39;s et al RT-PCR method &#40;Human Press Inc&#46;&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">&#58; RAR&#225;&#47;PML rearrangement was detected in 90&#37; &#40;20&#47;22&#41; of the patients at diagnosis positivesfor PML&#47;RAR&#225;&#46; RAR&#225;&#47;PML was detected in 74&#37;&#40;14&#47;19&#41; of post-induction samples versus37&#37; &#40;7&#47;19&#41; of positives for PML&#47;RAR&#225;&#46; Likewise RAR&#225;&#47;PML rearrangement was detected in somepost-consolidation samples &#40;2&#47;11&#41; that all were PMI&#47;RAR&#225; negatives&#46; In patients in maintenanceregimen a greater proportion of RAR&#225;&#47;PML positives &#40;6&#47;28&#41; versus PML&#47;RAR&#225; &#40;2&#47;28&#41; were observed&#46;In a patient in complete remission RAR&#225;&#47;PML preceded the positivity of PML&#47;RAR&#225; and persistedafter PMI&#47;RAR&#225; negativization&#46; The results of the patients monitored since the diagnosisshowed that RAR&#225;&#47;PML revert to negative one month after PML&#47;RAR&#225; negativization&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">&#58; RAR&#225;&#47;PML rearrangement is not expressed in the totality of the APL patients&#44; butin only a 90&#37; of them&#46; RAR&#225;&#47;PML rearrangement was detected in a greater proportion of samplesthan PML&#47;RAR&#225;&#46; RAR&#225;&#47;PML rearrangement lasted longer than PML&#47;RAR&#225; after treatment&#46;</p>"
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ISSN: 00257753
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