title: Aberrant BCR-ABL transcript with intronic insertion in a patient with philadelphia chromosome-positive chronic myeloid leukemia: implications for disease progression.
abstract: The BCR-ABL fusion gene is important for the leukemogenesis of chronic myeloid 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 insert. A 26-year-old woman was diagnosed as having Philadelphia chromosome (Ph) positive CML. Reverse transcription polymerase chain reaction detected an atypically large BCR-ABL mRNA transcript. Sequencing revealed a 589bp insertion consisting of a 5' portion of BCR intron b2 and a 3' portion of ABL intron 1b between BCR exon b2 and ABL exon a2. Although the typical b2a2 transcript was undetectable initially, it appeared after intensive chemotherapy. The aberrant transcript presumably arose as a result of a lack of splicing, and chemotherapy might modify the disease course by selecting the subpopulation of the CML clone expressing typical BCR-ABL mRNA dominantly.
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. mshira@tsurumi.beppu.kyushu-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Shiratsuchi
authors.forename: K
authors.initials: K
authors.lastname: Muta
authors.forename: R
authors.initials: R
authors.lastname: Minami
authors.forename: S
authors.initials: S
authors.lastname: Motomura
authors.forename: Y
authors.initials: Y
authors.lastname: Suehiro
authors.forename: Y
authors.initials: Y
authors.lastname: Abe
authors.forename: S
authors.initials: S
authors.lastname: Shiokawa
authors.forename: T
authors.initials: T
authors.lastname: Umemura
authors.forename: T
authors.initials: T
authors.lastname: Fukui
authors.forename: J
authors.initials: J
authors.lastname: Nishimura
authors.forename: H
authors.initials: H
authors.lastname: Nawata
mesh_terms: D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000235:genetics*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl