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

Abstract

Chronic myeloid leukemia (CML) is associated with several breakpoint regions that result in different BCR::ABL1 fusion transcripts. These include the major breakpoint region (M-BCR), minor breakpoint region (m-BCR), and mu breakpoint region (u-BCR) corresponding to p210, p190, and p230 fusion transcripts, respectively. This patient is a 38-year-old female with a new diagnosis of CML in chronic phase. A novel p210 fusion transcript splice variant was detected with qualitative reverse transcription PCR and capillary electrophoresis. Subsequent FISH study was performed, which revealed 86.5% positive for the BCR::ABL1 fusion. Quantitative real-time polymerase chain reaction (PCR) showed a negative result for the p210 fusion transcript. The variant was further characterized by Sanger sequencing. This variant is in-frame and predicted to be functional. This case illustrates the need for a combination of different testing techniques to fully characterize the rare BCR::ABL1 fusion transcripts.

Figure 1

The qualitative reverse transcription PCR shows a positive p210 variant (arrow).

Figure 2

Break-apart FISH test using the BCR probe (green) and the ABL1 probe (orange) reveals a rearrangement with the two genes.

Figure 3

The sequence had been run through BLAST and ENSEMBL software programs. This portion of the electropherogram displays the site between exon 13 from the BCR gene and exon 2 of the ABL1 gene. The eight additional nucleotides–AACCCAAG–detected between the BCR and ABL1 are shown. The sequence AAGCCC is noted to be the first six nucleotides for the ABL1 gene.