Research paperA rare e13a3 (b2a3) BCR-ABL1 fusion transcript with normal karyotype in chronic myeloid leukemia: The challenges in diagnosis and monitoring minimal residual disease (MRD)

- A patient with CML who tested both negative by RT-PCR and cytogenetic analysis was reported.
- FISH showed cryptic insertion of ABL into BCR gene on chromosome 22.
- DNA sequencing with alternative primer sets demonstrated the presence of an e13a3 BCR-ABL fusion.
- FISH analysis demonstrated a markedly reduced BCR-ABL1 fusion rate of 0 after 6 months imatinib treatment.

Patients with chronic myeloid leukemia (CML) have a t (9;22)(q34;q11.2) or variant translocation that results in a BCR-ABL1 fusion gene. For many years, conventional karyotyping has been used as the standard diagnostic tool for t (9;22) (q34;q11.2). However, it has several limitations that may lead to failure for detecting BCR-ABL1 gene rearrangements in around 5% of all CML patients. Although reverse transcription polymerase chain reaction (RT-PCR) has evolved as a sensitive method for detecting BCR-ABL1 translocation, this method fail to detect certain BCR-ABL1 fusion transcript type, such as e13a3 (also known as b2a3), as a result of many commercially available and laboratory-developed primer sets. Fortunately, these two rare situations rarely appear at the same time, therefore, the combination of two methods rarely misdiagnosed the patients with CML. In this study, we report a patient with CML who tested both negative by RT-PCR and cytogenetic analysis at the time of diagnosis. She was diagnosed as atypical CML (aCML) and allogeneic hematopoietic stem cell transplantation was suggested. Further fluorescence in situ hybridization (FISH) showed cryptic insertion of ABL into BCR gene on chromosome 22, and DNA sequencing with alternative primer sets demonstrated the presence of an e13a3 BCR-ABL1 fusion. She was diagnosed as CML and received imatinib 400 mg/day. A follow-up BCR-ABL1 FISH analysis demonstrated a markedly reduced BCR-ABL1 fusion rate of 0 after 6 months treatment, indicating a complete cytogenetic response.