Novel BCR-ABL1 fusion identified by targeted next-generation sequencing in a patient with an atypical myeloproliferative neoplasm

SummaryAn unusual case of a BCR-ABL1-positive myeloproliferative neoplasm is presented with discordant molecular and cytogenetic characterization at diagnosis. More extensive molecular characterization of the fusion messenger RNA transcript using a next-generation sequencing approach identified a novel BCR-calcineurin-binding protein 1-ABL1 variant, which has not been described previously. This case highlights the potential utility of next-generation sequencing for a single-target application to resolve rare and unusual tumor genetic variants when standard molecular diagnostic methods are inconclusive. Although the relationship of this novel BCR-ABL1 fusion to the atypical pathologic features and initially suboptimal therapeutic response profile remains speculative, this case indicates that accurate molecular characterization of rare variants has diagnostic and potentially prognostic relevance.