Relationship of the BCR gene breakpoint and the type of BCR/ABL transcript to clinical course, prognostic indexes and survival in patients with chronic myeloid leukemia

Med Sci Monit. 2002 May;8(5):BR193-7.

Abstract

Background: Chronic myeloid leukemia is characterized by the presence of the Philadelphia chromosome. At the molecular level a fusion of part of the ABL and BCR genes is observed. The breakpoint locations in the BCR gene fall between exons b2a2 or b3a2 (5' and 3', respectively). Depending on the BCR gene breakpoint two types of mRNA are created. Differences in the types of transcripts and/or the breakpoint site may have an influence on the clinical course of the disease. This prompted the present author to separate subtypes of chronic myeloid leukemia on the molecular level.

Material/methods: 71 patients diagnosed with chronic myeloid leukemia in the chronic phase were enrolled in the study. In 61 patients the type of BCR/ABL transcript was determined, and in 27 patients BCR breakpoints were established. Possible correlations between the clinical course, prognostic indexes, survival and the type of transcript and breakpoint were examined.

Results: No correlation between the clinical course, prognostic index, or survival was observed in patients with 5' and 3' breakpoints. The patients with b3a2 transcript experienced longer survival than the patients expressing b2a2 transcript. However, no significant differences were observed in the duration of the chronic phase between the two groups.

Conclusions: The type of BCR gene breakpoint seems to have no prognostic value in patients with chronic myeloid leukemia. The longer survival of patients expressing the b3a2 transcript may be caused by the less aggressive course of the accelerated or blastic phase.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • DNA Damage
  • Female
  • Fusion Proteins, bcr-abl / metabolism*
  • Genes, abl / genetics*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Treatment Outcome

Substances

  • RNA, Messenger
  • Fusion Proteins, bcr-abl