The Recurrent Atypical e8a2 <i>BCR::ABL1</i> Transcript with Insertion of an Inverted 55 Base Pair <i>ABL1</i> Intron 1b Sequence: A Detailed Molecular Analysis

Abstract

Atypical <i>BCR::ABL1</i> transcripts are found in approximately 2% of cases of chronic myeloid leukemia. It is important to detect them since affected patients also benefit from tyrosine kinase inhibitor therapy. In the rare e8a2 atypical <i>BCR::ABL1</i> transcript, two out-of-frame exons are fused, thus, interposed nucleotides are usually found at the fusion site to restore the reading frame. In approximately half of previously reported e8a2 <i>BCR::ABL1</i> cases, an inserted 55 bp sequence homologous to an inverted sequence from <i>ABL1</i> intron 1b was detected. The generation of this recurrent transcript variant is not obvious. This work describes the molecular analysis of such an e8a2 <i>BCR::ABL1</i> translocation from a CML patient. The genomic chromosomal breakpoint is identified, and the formation of this transcript is theoretically explained. The clinical course of the patient is reported, and recommendations are provided for the molecular analysis of future e8a2 <i>BCR::ABL1</i> cases.