title: Detection of two alternative bcr/abl mRNA junctions and minimal residual disease in Philadelphia chromosome positive chronic myelogenous leukemia by polymerase chain reaction.
abstract: The Philadelphia (Ph') chromosome in chronic myelogenous leukemia (CML) results in fusion of the bcr gene and c-abl oncogene, which transcribes into two types of chimeric bcr/abl mRNAs: the L-6 junction and the K-28 junction. By means of a highly sensitive assay, combination of reverse transcription and polymerase chain reaction (RT/PCR), we analyzed 38 blood samples obtained from 31 patients with Ph'-positive CML and two patients with Ph'-negative bcr rearranged CML. Among the 21 samples obtained in chronic phase, eight patients had the L-6 mRNA, 11 had the K-28 mRNA, and two had both the L-6 and K-28 mRNAs. Among the nine samples obtained in blast crisis, four contained the L-6 mRNA, two contained the K-28 mRNA, and three contained both the K-28 and L-6 mRNAs. This finding supports the concept of alternative splicing of bcr/abl mRNAs transcribed in Ph'-positive CML. However, it appears to be a rare event. Of the eight samples obtained from eight patients who had achieved complete cytogenetic remission and negativity for bcr region rearrangement for 6 months to 3 years after recombinant alpha interferon (r alpha-IFN) therapy, all of them showed evidence of minimal residual Ph'-positive clones as detected by the RT/PCR assay. This finding suggests that interferon therapy suppresses the proliferation of the Ph'-positive clones, but it does not completely eradicate the Ph'-positive stem cells.
authors.affiliation: Department of Hematology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
authors.forename: M S
authors.initials: MS
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: LeMaistre
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: M
authors.initials: M
authors.lastname: Talpaz
authors.forename: E J
authors.initials: EJ
authors.lastname: Freireich
authors.forename: J M
authors.initials: JM
authors.lastname: Trujillo
authors.forename: S A
authors.initials: SA
authors.lastname: Stass
mesh_terms: D004259:DNA-Directed DNA Polymerase; D005784:Gene Amplification; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000628:therapy; D015345:Oligonucleotide Probes; D011519:Proto-Oncogenes; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D011994:Recombinant Proteins; D012074:Remission Induction; D019914:Taq Polymerase; D014158:Transcription, Genetic
chemical_list: D007370:Interferon Type I; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019914:Taq Polymerase; D004259:DNA-Directed DNA Polymerase