title: Dual transcription of b2a2 and b3a2 BCR-ABL transcripts in chronic myeloid leukaemia is confined to patients with a linked polymorphism within the BCR gene.
abstract: We propose a mechanism for dual expression of b2a2 and b3a2 BCR-ABL in chronic myeloid leukaemia (CML). We have identified a BCR allele, present in approximately 29% of the population, which includes an adenine to guanine polymorphism in the putative branchpoint of BCR intron 13. CML patients who expressed both b2a2 and b3a2 transcripts had the allele, which was also associated with alternative transcription of the normal BCR allele. We conclude that the BCR intronic polymorphism is associated with activation of a cryptic branchpoint resulting in reduced efficiency of RNA splicing and exon 14 (b3) skipping in BCR and BCR-ABL.
authors.affiliation: Division of Molecular Pathology, Institute of Medical and Veterinary Science, Box 14, Rundle Mall, Adelaide, SA 5000, Australia. susan.branford@imvs.sa.gov.au
authors.forename: Susan
authors.initials: S
authors.lastname: Branford
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Hughes
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Rudzki
mesh_terms: D017398:Alternative Splicing; D005091:Exons; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D007438:Introns; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051562:Proto-Oncogene Proteins c-bcr; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr