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.
| Original language | English |
|---|---|
| Pages (from-to) | 60-65 |
| Number of pages | 6 |
| Journal | Genes Chromosomes and Cancer |
| Volume | 58 |
| Issue number | 1 |
| DOIs | |
| Publication status | E-pub ahead of print - Dec 4 2018 |
Fingerprint
Cite this
Identification and monitoring of atypical PML/RARA fusion transcripts in acute promyelocytic leukemia. / Iaccarino, Licia; Divona, Mariadomenica; Ottone, Tiziana; Cicconi, Laura; Lavorgna, Serena; Ciardi, Claudia; Alfonso, Valentina; Travaglini, Serena; Facchini, Luca; Cimino, Giuseppe; Di Bona, Eros; Voso, Maria Teresa; Lo-Coco, Francesco.
In: Genes Chromosomes and Cancer, Vol. 58, No. 1, 04.12.2018, p. 60-65.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Identification and monitoring of atypical PML/RARA fusion transcripts in acute promyelocytic leukemia
AU - Iaccarino, Licia
AU - Divona, Mariadomenica
AU - Ottone, Tiziana
AU - Cicconi, Laura
AU - Lavorgna, Serena
AU - Ciardi, Claudia
AU - Alfonso, Valentina
AU - Travaglini, Serena
AU - Facchini, Luca
AU - Cimino, Giuseppe
AU - Di Bona, Eros
AU - Voso, Maria Teresa
AU - Lo-Coco, Francesco
N1 - © 2018 Wiley Periodicals, Inc.
PY - 2018/12/4
Y1 - 2018/12/4
N2 - 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.
AB - 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.
U2 - 10.1002/gcc.22708
DO - 10.1002/gcc.22708
M3 - Article
C2 - 30421475
VL - 58
SP - 60
EP - 65
JO - Genes Chromosomes and Cancer
JF - Genes Chromosomes and Cancer
SN - 1045-2257
IS - 1
ER -