title: Novel types of bcr-abl transcript with breakpoints in BCR exon 8 found in Philadelphia positive patients with typical chronic myeloid leukemia retain the sequence encoding for the DBL- and CDC24 homology domains but not the pleckstrin homology one.
abstract: OBJECTIVE
  We previously described a novel type of the chimeric bcr-abl mRNA transcript in a patient with a Philadelphia chromosome positive chronic myeloid leukemia. A similar bcr-abl transcript has also been described by others.
  
  
  METHODS
  Sequence analysis of the fusion region showed a join between part of exon e8 of the bcr gene and an intronic sequence of abl intron 1b spliced on exon a2 of the abl gene, giving rise to an in-frame e8-int-a2 bcr-abl transcript, translated into a 197.5 kDa BCR-ABL protein of 1804 amino acid residues, which we named p200 BCR-ABL.
  
  
  RESULTS
  In this work, employing protein comparison analysis (pFAM) we show that these novel bcr-abl transcripts retain the DBL homology (DH) domain and the recently recognized CDC24 homology domain, but not the pleckstrin homology (PH) domain of the bcr gene.
  
  
  CONCLUSIONS
  This observation, along with the myeloid immunophenotype of the tumor and, at least in one case, the patient's correspondingly good response to alpha-interferon therapy, suggests that p200 BCR-ABL is more similar to p210 BCR-ABL, in which the DH, CDC24 and PH domains are all maintained, than to p185, in which these domains are all lost.
authors.affiliation: Molecular Biology Unit, Institute of Hematology and Medical Oncology L. e A. Seràgnoli, University of Bologna, via Massarenti 9, 40138 Bologna, Italy. gmartino@kaiser.alma.unibo.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Marilina
authors.initials: M
authors.lastname: Amabile
authors.forename: Barbara
authors.initials: B
authors.lastname: Giannini
authors.forename: Carolina
authors.initials: C
authors.lastname: Terragna
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ottaviani
authors.forename: Simona
authors.initials: S
authors.lastname: Soverini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019457:Chromosome Breakage / Q000235:genetics*; D005091:Exons; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics; D017421:Sequence Analysis
chemical_list: D012333:RNA, Messenger; D016044:Fusion Proteins, bcr-abl