Coexistent Out-of-frame and In-frame e8a2 <i>BCR</i>::<i>ABL1</i> Transcripts in a Patient with Chronic Myeloid Leukemia: A Case Report

Among atypical BCR::ABL1 fusions, e8a2 fusion joins BCR exon 8 and ABL1 exon 2. Because the reading frames of these exons do not interlock, e8a2 fusion requires additional alterations to produce in-frame fusion transcripts and functional fusion proteins.Nevertheless, there have been rare cases in which only out-of-frame e8a2 fusion transcripts were detectable.The reason why these patients exhibit clinical courses consistent with BCR::ABL1 fusion, despite the predicted absence of functional fusion proteins, remains unclear.Herein, we report a case of chronic myeloid leukemia with e8a2 BCR::ABL1 fusion, in which whole-transcriptome sequencing identified out-of-frame e8a2 fusion transcripts coexistent with inframe transcripts.The out-of-frame transcripts had no additional alterations, whereas the in-frame transcripts had an insertion of a 55-bp sequence originating from inverted ABL1 intron 1.This case indicates that the detection of an out-of-frame e8a2 BCR::ABL1 fusion transcript does not completely rule out a functional in-frame BCR::ABL1 fusion.