Once the diagnostic suspicion of acute promyelocytic leukemia (APL) has been raised, international guidelines recommend prompt initiation of tailored therapy and supportive care, while awaiting for genetic confirmation of the diagnosis, and the identification of the specific PML/RARA isoform by reverse transcriptase polymerase chain reaction (RT-PCR). Depending on the PML break point, usually located within intron 6, exon 6, or intron 3, different PML/RARA transcript isoforms may be generated, that is, long (bcr1), variant (bcr2), and short (bcr3), respectively. We report here the characterization of three APL cases harboring atypical PML/RARA transcripts, which were not clearly detectable after standard RT-PCR amplification. In all three cases, clinical, morphological, and immunophenotypic features were consistent with APL. Direct sequencing allowed the identification of atypical break points within the PML and RARA genes. Then, we designed a patient-specific quantitative real-time PCR for the atypical transcripts, which allowed for specific quantitative evaluation of minimal residual disease (MRD) during follow-up. Despite the rarity of APL cases with an atypical PML/RARA fusion, our study indicates that an integrated laboratory approach, employing several diagnostic techniques is crucial to timely diagnose APL. This approach allows prompt initiation of specific targeted treatment and reliable MRD monitoring in atypical APL cases.

Iaccarino, L., Divona, M., Ottone, T., Cicconi, L., Lavorgna, S., Ciardi, C., et al. (2019). Identification and monitoring of atypical PML/RARA fusion transcripts in acute promyelocytic leukemia. GENES, CHROMOSOMES & CANCER, 58(1), 60-65 [10.1002/gcc.22708].

Identification and monitoring of atypical PML/RARA fusion transcripts in acute promyelocytic leukemia

Iaccarino L.
Writing – Original Draft Preparation
;
Ottone T.
Writing – Original Draft Preparation
;
Lavorgna S.
Methodology
;
Alfonso V.
Writing – Original Draft Preparation
;
Voso M. T.;Lo-Coco F.
2019-01-01

Abstract

Once the diagnostic suspicion of acute promyelocytic leukemia (APL) has been raised, international guidelines recommend prompt initiation of tailored therapy and supportive care, while awaiting for genetic confirmation of the diagnosis, and the identification of the specific PML/RARA isoform by reverse transcriptase polymerase chain reaction (RT-PCR). Depending on the PML break point, usually located within intron 6, exon 6, or intron 3, different PML/RARA transcript isoforms may be generated, that is, long (bcr1), variant (bcr2), and short (bcr3), respectively. We report here the characterization of three APL cases harboring atypical PML/RARA transcripts, which were not clearly detectable after standard RT-PCR amplification. In all three cases, clinical, morphological, and immunophenotypic features were consistent with APL. Direct sequencing allowed the identification of atypical break points within the PML and RARA genes. Then, we designed a patient-specific quantitative real-time PCR for the atypical transcripts, which allowed for specific quantitative evaluation of minimal residual disease (MRD) during follow-up. Despite the rarity of APL cases with an atypical PML/RARA fusion, our study indicates that an integrated laboratory approach, employing several diagnostic techniques is crucial to timely diagnose APL. This approach allows prompt initiation of specific targeted treatment and reliable MRD monitoring in atypical APL cases.
2019
In corso di stampa
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/15 - Malattie del Sangue
English
APL; atypical PML/RARA; real-time PCR; Adult; Aged; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 17; Exons; Female; Humans; Introns; Karyotyping; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Neoplasm, Residual; Oncogene Proteins, Fusion; Promyelocytic Leukemia Protein; Retinoic Acid Receptor alpha
Iaccarino, L., Divona, M., Ottone, T., Cicconi, L., Lavorgna, S., Ciardi, C., et al. (2019). Identification and monitoring of atypical PML/RARA fusion transcripts in acute promyelocytic leukemia. GENES, CHROMOSOMES & CANCER, 58(1), 60-65 [10.1002/gcc.22708].
Iaccarino, L; Divona, M; Ottone, T; Cicconi, L; Lavorgna, S; Ciardi, C; Alfonso, V; Travaglini, S; Facchini, L; Cimino, G; Di Bona, E; Voso, Mt; Lo-Coco, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/211914
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