Aberrant BCR-ABL transcript with intronic insertion in a patient with Philadelphia chromosome-positive chronic myeloid leukemia: Implications for disease progression

The BCR-ABL fusion gene is important for the leukemogenesis of chronic myel oid leukemia (CML). A relationship between types of BCR-ABL transcripts in CML and clinical features has been proposed. We present here a patient with CML who carried an aberrant BCR-ABL transcript With an intronic sequence i nsert. A 26-year-old woman was diagnosed os having Philadelphia chromosome (Ph) positive CML. Reverse transcription polymerase chain reaction detected an atypically large BCR-ABL mRNA transcript. Sequencing revealed a 589bp i nsertion consisting of a 5' portion of BCR intron b2 and a 3' portion of AB L intron Ib between BCR exon b2 and ABL exon a2. Although the typical b2a2 transcript was undetectable initially, it appeared after intensive chemothe rapy. The aberrant transcript presumably arose as a result of a lack of spl icing, and chemotherapy might modify the disease course by selecting the su bpopulation of the CML clone expressing typical BCR-ABL mRNA dominantly.