BCR–ABL1 e6a2 transcript in chronic myeloid leukemia: biological features and molecular monitoring by droplet digital PCR
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The BCR–ABL1 fusion on the Philadelphia (Ph) chromosome is a hallmark of chronic myeloid leukemia (CML). More than 95 % of BCR–ABL1 transcripts in CML are either e13a2 or e14a2 (major breakpoint cluster region or M-bcr), whereas rare BCR–ABL1 transcripts are occasionally observed, accounting for less than 1 % of CML cases. Among these, a very rare fusion transcript joining the first 6 exons of BCR to exon 2 of ABL1 (e6a2) has been reported in various hematological malignancies characterized by an aggressive clinical course. We report a new case of blast crisis (BC) CML with an e6a2 fusion transcript characterized by many eosinophil precursors with abnormal granules. Moreover, fluorescence in situ hybridization analysis revealed genomic deletions of 1.3 megabases and 342 kilobases on der(9) of chromosome 9 and 22 sequences, respectively. The fusion transcript was quantified at diagnosis and during follow-up using digital droplet polymerase chain reaction (ddPCR) technology. The patient was treated with Dasatinib (140 mg/day), resulting in a 3-log reduction of the e6a2 transcript molecular burden from the third month after treatment. In this twentieth e6a2 case, characterized by marked eosinophilic dysplasia, deletions on der(9), and responsive to tyrosine kinase inhibitors therapy, we demonstrate that for molecular response monitoring of rare fusion transcripts associated with CML, ddPCR is a very useful technology.
KeywordsChronic myeloid leukemia BCR–ABL1 e6a2 transcript Digital droplet polymerase chain reaction Eosinophilic dysplasia Genomic microdeletions
The authors would like to thank Ms. MVC Pragnell, B.A., for language revision of the manuscript.
This work was supported by “Fondazione Cassa di Risparmio di Puglia” and “Associazione Italiana contro le Leucemie (AIL)-BARI”.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
This study was performed in agreement with the Declaration of Helsinki and approved by the local Ethical Committee (Comitato Etico Indipendente Locale, Azienda Ospedaliera “Ospedale Policlinico Consorziale” di Bari, Regione Puglia). Written informed consent was obtained from the patient; a copy of written consents is available for review by the Editor of this journal.
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