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

Autor: Laura Cicconi, Francesco Lo-Coco, Giuseppe Cimino, Mariadomenica Divona, Valentina Alfonso, Eros Di Bona, Licia Iaccarino, Serena Travaglini, Luca Facchini, Maria Teresa Voso, Tiziana Ottone, Serena Lavorgna, Claudia Ciardi
Rok vydání: 2018
Předmět:
Male
Cancer Research
Neoplasm
Residual
Oncogene Proteins
Fusion
Promyelocytic Leukemia Protein
law.invention
Exon
0302 clinical medicine
Leukemia
Promyelocytic
Acute
law
Polymerase chain reaction
Promyelocytic
Oncogene Proteins
Leukemia
Retinoic Acid Receptor alpha
breakpoint cluster region
Exons
Middle Aged
Real-time polymerase chain reaction
Residual
030220 oncology & carcinogenesis
Female
Human
Acute promyelocytic leukemia
Adult
atypical PML/RARA
Acute
Biology
Chromosomes
03 medical and health sciences
Genetics
medicine
Humans
APL
real-time PCR
Aged
Chromosomes
Human
Pair 15
Chromosomes
Human
Pair 17
Introns
Karyotyping
Fusion
Pair 17
Pair 15
Intron
medicine.disease
Minimal residual disease
Reverse transcriptase
apl
atypical pml/rara
real-time pcr
adult
aged
chromosomes
human
pair 15
chromosomes
human
pair 17
exons
female
humans
introns
karyotyping
leukemia
Cancer research
Neoplasm
Settore MED/15 - Malattie del Sangue
Zdroj: Genes, chromosomescancer. 58(1)
ISSN: 1098-2264
Popis: 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.
Databáze: OpenAIRE
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