A Novel BCR::ABL1 Variant Detected with Multiple Testing Modalities.

Area of Science:

• Hematology
• Molecular Biology
• Oncology

Background:

• Chronic myeloid leukemia (CML) is characterized by specific BCR::ABL1 fusion transcripts arising from different breakpoint regions (M-BCR, m-BCR, u-BCR).
• These breakpoints correspond to distinct fusion protein types: p210, p190, and p230.

Observation:

• A novel p210 fusion transcript splice variant was detected in a newly diagnosed CML patient using qualitative reverse transcription PCR and capillary electrophoresis.
• Fluorescence in situ hybridization (FISH) confirmed 86.5% positivity for the BCR::ABL1 fusion.

Findings:

• Quantitative real-time PCR yielded a negative result for the p210 fusion transcript, contrasting with the qualitative findings.
• Sanger sequencing revealed the variant to be in-frame and predicted to be functional.

Implications:

• This case underscores the necessity of employing a combination of diagnostic techniques for comprehensive characterization of rare BCR::ABL1 fusion transcripts.
• Accurate identification of fusion transcript variants is crucial for precise CML diagnosis and potentially tailored therapeutic strategies.