Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem
Acute promyelocytic leukemia lacking t(15;17): Molecular evidence of atypical PML/RAR-α transcriptional variant by gene sequencing
Authors
Đorđević, VesnaTošić, Nataša
Denčić-Fekete, Marija
Virijević, Marijana
Jovanović, Jelica
Jaković, Ljubomir
Kraguljac-Kurtović, Nada
Bogdanović, Andrija
Kostić, Tatjana
Pavlović, Sonja
Article (Published version)
Metadata
Show full item recordAbstract
Uvod. Precizno dijagnostikovanje akutne promijelocitne leukemije (APL), ne samo na osnovu morfoloških i kliničkih parametara, već i na molekularnom nivou, veoma je važno radi primene adekvatne ciljane terapije. Prikaz bolesnika. Prikazali smo bolesnicu, staru 62 godine, sa dijagnozom APL. Primenom standardne citogenetičke analize, kao i primenom fluorescentne in situ hibridizacije (FISH), nije bilo potvrđeno prisustvo t(15;17) kod opisane bolesnice. Primenom metode reverzna transkriptazalančana reakcija polimeraze (RT-PCR), identifikovana su dva atipična promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fuziona transkripta. Oba transkripta su predstavljala izoforme. Duži transkript je zadržao "okvir čitanja" i kodirao je funkcionalan PML/RAR-α aberantni protein, dok je kraći transkript bio van "okvira čitanja". Zaključak. Naša studija ukazuje na potrebu za primenom molekularne metodologije u svakodnevnoj kliničkoj praksi. Precizna karakterizacija PML/RAR-α fuzionih transkip...ta čini osnovu za identifikovanje retkih bolesnika čije lečenje zahteva dodatni oprez. Prema našim saznanjima, ovo je tek peti slučaj opisanog atipičnog PML/RAR-α transkripta koji u sebi sadrži celokupan PML egzon 7a, a među njima jedini koji se nije mogao detektovati primenom citogenetičke i FISH analize. Svi ovde predstavljeni slučajevi su imali smrtni ishod. Zbog toga, naši rezulatati, zajedno sa sličnim slučajevima opisanim u literaturi, naglašavaju značaj detaljne identifikacije atipičnih PML/RAR-α fuzija, ne samo u svrhu prepoznavanja njihove uloge u procesu leukemogeneze, veći i u smislu procene njihovog uticaja na ishod lečenja.
Introduction. The accurate diagnosis of acute promyelocytic leukemia (APL), not only on the morphological and clinical, but also on the molecular level, is very important for application of targeted therapies. Case report. A 62year-old woman presented with APL. By using conventional cytogenetic analysis as well as applying the fluorescence in situ hybridization (FISH) analysis it has not been possible to confirm the presence of t(15;17) in the presented patient. Using reverse transcriptase polymerase chain reaction (RT-PCR) two atypical promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fusion transcripts were identified. Both detected transcripts were isoforms. The larger transcript was in-frame, coding for functional aberrant PML/RAR-α protein, while the shorter transcript was an out-of-frame. Conclusion. Our study highlights the need for the application of molecular methodology in daily clinical practice. Precise characterization of PML/RAR-α fusion transcript creates a b...asis for identifying rare individual cases that require special caution when treating such patients. To our knowledge this is only the fifth case of atypical PML/RAR-α transcript containing full PML exon 7a, and among them the only one that was cytogenetically cryptic and FISH negative. All of the herein presented cases had lethal outcome. Therefore, our findings with the additional review of the literature, emphasizes the importance of detailed identification of atypical PML/RAR-α fusions, not only for the purpose of knowing their role in leukemogenesis, but also for the assessment of the impact that they can have on the outcome of the treatment.
Keywords:
polimeraza, reakcija stvaranja lanaca, reverzna transkripcija / leukemija, promijelocitna, akutna / hibridizacija in situ, fluorescentna / dijagnoza / biologija, molekularna / reverse transcriptase polymerase chain reaction / molecular biology / leukemia, promyelocytic, acute / in situ hibridization, fluorescence / diagnosisSource:
Vojnosanitetski pregled, 2020, 77, 1, 97-102Publisher:
- Vojnomedicinska akademija - Institut za naučne informacije, Beograd
Funding / projects:
- Rare Diseases:Molecular Pathophysiology, Diagnostic and Therapeutic Modalities and Social, Ethical and Legal Aspects (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41004)
DOI: 10.2298/VSP170620040D
ISSN: 0042-8450
WoS: 000513552500015
Scopus: 2-s2.0-85056474116
Collections
Institution/Community
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Đorđević, Vesna AU - Tošić, Nataša AU - Denčić-Fekete, Marija AU - Virijević, Marijana AU - Jovanović, Jelica AU - Jaković, Ljubomir AU - Kraguljac-Kurtović, Nada AU - Bogdanović, Andrija AU - Kostić, Tatjana AU - Pavlović, Sonja PY - 2020 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1371 AB - Uvod. Precizno dijagnostikovanje akutne promijelocitne leukemije (APL), ne samo na osnovu morfoloških i kliničkih parametara, već i na molekularnom nivou, veoma je važno radi primene adekvatne ciljane terapije. Prikaz bolesnika. Prikazali smo bolesnicu, staru 62 godine, sa dijagnozom APL. Primenom standardne citogenetičke analize, kao i primenom fluorescentne in situ hibridizacije (FISH), nije bilo potvrđeno prisustvo t(15;17) kod opisane bolesnice. Primenom metode reverzna transkriptazalančana reakcija polimeraze (RT-PCR), identifikovana su dva atipična promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fuziona transkripta. Oba transkripta su predstavljala izoforme. Duži transkript je zadržao "okvir čitanja" i kodirao je funkcionalan PML/RAR-α aberantni protein, dok je kraći transkript bio van "okvira čitanja". Zaključak. Naša studija ukazuje na potrebu za primenom molekularne metodologije u svakodnevnoj kliničkoj praksi. Precizna karakterizacija PML/RAR-α fuzionih transkipta čini osnovu za identifikovanje retkih bolesnika čije lečenje zahteva dodatni oprez. Prema našim saznanjima, ovo je tek peti slučaj opisanog atipičnog PML/RAR-α transkripta koji u sebi sadrži celokupan PML egzon 7a, a među njima jedini koji se nije mogao detektovati primenom citogenetičke i FISH analize. Svi ovde predstavljeni slučajevi su imali smrtni ishod. Zbog toga, naši rezulatati, zajedno sa sličnim slučajevima opisanim u literaturi, naglašavaju značaj detaljne identifikacije atipičnih PML/RAR-α fuzija, ne samo u svrhu prepoznavanja njihove uloge u procesu leukemogeneze, veći i u smislu procene njihovog uticaja na ishod lečenja. AB - Introduction. The accurate diagnosis of acute promyelocytic leukemia (APL), not only on the morphological and clinical, but also on the molecular level, is very important for application of targeted therapies. Case report. A 62year-old woman presented with APL. By using conventional cytogenetic analysis as well as applying the fluorescence in situ hybridization (FISH) analysis it has not been possible to confirm the presence of t(15;17) in the presented patient. Using reverse transcriptase polymerase chain reaction (RT-PCR) two atypical promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fusion transcripts were identified. Both detected transcripts were isoforms. The larger transcript was in-frame, coding for functional aberrant PML/RAR-α protein, while the shorter transcript was an out-of-frame. Conclusion. Our study highlights the need for the application of molecular methodology in daily clinical practice. Precise characterization of PML/RAR-α fusion transcript creates a basis for identifying rare individual cases that require special caution when treating such patients. To our knowledge this is only the fifth case of atypical PML/RAR-α transcript containing full PML exon 7a, and among them the only one that was cytogenetically cryptic and FISH negative. All of the herein presented cases had lethal outcome. Therefore, our findings with the additional review of the literature, emphasizes the importance of detailed identification of atypical PML/RAR-α fusions, not only for the purpose of knowing their role in leukemogenesis, but also for the assessment of the impact that they can have on the outcome of the treatment. PB - Vojnomedicinska akademija - Institut za naučne informacije, Beograd T2 - Vojnosanitetski pregled T1 - Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem T1 - Acute promyelocytic leukemia lacking t(15;17): Molecular evidence of atypical PML/RAR-α transcriptional variant by gene sequencing EP - 102 IS - 1 SP - 97 VL - 77 DO - 10.2298/VSP170620040D ER -
@article{ author = "Đorđević, Vesna and Tošić, Nataša and Denčić-Fekete, Marija and Virijević, Marijana and Jovanović, Jelica and Jaković, Ljubomir and Kraguljac-Kurtović, Nada and Bogdanović, Andrija and Kostić, Tatjana and Pavlović, Sonja", year = "2020", abstract = "Uvod. Precizno dijagnostikovanje akutne promijelocitne leukemije (APL), ne samo na osnovu morfoloških i kliničkih parametara, već i na molekularnom nivou, veoma je važno radi primene adekvatne ciljane terapije. Prikaz bolesnika. Prikazali smo bolesnicu, staru 62 godine, sa dijagnozom APL. Primenom standardne citogenetičke analize, kao i primenom fluorescentne in situ hibridizacije (FISH), nije bilo potvrđeno prisustvo t(15;17) kod opisane bolesnice. Primenom metode reverzna transkriptazalančana reakcija polimeraze (RT-PCR), identifikovana su dva atipična promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fuziona transkripta. Oba transkripta su predstavljala izoforme. Duži transkript je zadržao "okvir čitanja" i kodirao je funkcionalan PML/RAR-α aberantni protein, dok je kraći transkript bio van "okvira čitanja". Zaključak. Naša studija ukazuje na potrebu za primenom molekularne metodologije u svakodnevnoj kliničkoj praksi. Precizna karakterizacija PML/RAR-α fuzionih transkipta čini osnovu za identifikovanje retkih bolesnika čije lečenje zahteva dodatni oprez. Prema našim saznanjima, ovo je tek peti slučaj opisanog atipičnog PML/RAR-α transkripta koji u sebi sadrži celokupan PML egzon 7a, a među njima jedini koji se nije mogao detektovati primenom citogenetičke i FISH analize. Svi ovde predstavljeni slučajevi su imali smrtni ishod. Zbog toga, naši rezulatati, zajedno sa sličnim slučajevima opisanim u literaturi, naglašavaju značaj detaljne identifikacije atipičnih PML/RAR-α fuzija, ne samo u svrhu prepoznavanja njihove uloge u procesu leukemogeneze, veći i u smislu procene njihovog uticaja na ishod lečenja., Introduction. The accurate diagnosis of acute promyelocytic leukemia (APL), not only on the morphological and clinical, but also on the molecular level, is very important for application of targeted therapies. Case report. A 62year-old woman presented with APL. By using conventional cytogenetic analysis as well as applying the fluorescence in situ hybridization (FISH) analysis it has not been possible to confirm the presence of t(15;17) in the presented patient. Using reverse transcriptase polymerase chain reaction (RT-PCR) two atypical promyelotic leukemia/retinoic acid receptor alpha (PML/RAR-α) fusion transcripts were identified. Both detected transcripts were isoforms. The larger transcript was in-frame, coding for functional aberrant PML/RAR-α protein, while the shorter transcript was an out-of-frame. Conclusion. Our study highlights the need for the application of molecular methodology in daily clinical practice. Precise characterization of PML/RAR-α fusion transcript creates a basis for identifying rare individual cases that require special caution when treating such patients. To our knowledge this is only the fifth case of atypical PML/RAR-α transcript containing full PML exon 7a, and among them the only one that was cytogenetically cryptic and FISH negative. All of the herein presented cases had lethal outcome. Therefore, our findings with the additional review of the literature, emphasizes the importance of detailed identification of atypical PML/RAR-α fusions, not only for the purpose of knowing their role in leukemogenesis, but also for the assessment of the impact that they can have on the outcome of the treatment.", publisher = "Vojnomedicinska akademija - Institut za naučne informacije, Beograd", journal = "Vojnosanitetski pregled", title = "Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem, Acute promyelocytic leukemia lacking t(15;17): Molecular evidence of atypical PML/RAR-α transcriptional variant by gene sequencing", pages = "102-97", number = "1", volume = "77", doi = "10.2298/VSP170620040D" }
Đorđević, V., Tošić, N., Denčić-Fekete, M., Virijević, M., Jovanović, J., Jaković, L., Kraguljac-Kurtović, N., Bogdanović, A., Kostić, T.,& Pavlović, S.. (2020). Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem. in Vojnosanitetski pregled Vojnomedicinska akademija - Institut za naučne informacije, Beograd., 77(1), 97-102. https://doi.org/10.2298/VSP170620040D
Đorđević V, Tošić N, Denčić-Fekete M, Virijević M, Jovanović J, Jaković L, Kraguljac-Kurtović N, Bogdanović A, Kostić T, Pavlović S. Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem. in Vojnosanitetski pregled. 2020;77(1):97-102. doi:10.2298/VSP170620040D .
Đorđević, Vesna, Tošić, Nataša, Denčić-Fekete, Marija, Virijević, Marijana, Jovanović, Jelica, Jaković, Ljubomir, Kraguljac-Kurtović, Nada, Bogdanović, Andrija, Kostić, Tatjana, Pavlović, Sonja, "Akutna promijelocitna leukemija bez t(15;17) - molekularni dokazi atipične PML/RAR-α transkripcione varijante genskim sekvenciranjem" in Vojnosanitetski pregled, 77, no. 1 (2020):97-102, https://doi.org/10.2298/VSP170620040D . .