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; 8(5): BR193-197
BACKGROUND: Chronic myeloid leukemia is characterized by the presence ofthe 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). Dependingon the BCR gene breakpoint two types of mRNA are created. Differences in the types of transcripts and/orthe breakpoint site may have an influence on the clinical course of the disease. This prompted the presentauthor to separate subtypes of chronic myeloid leukemia on the molecular level. MATERIAL/METHODS: 71patients diagnosed with chronic myeloid leukemia in the chronic phase were enrolled in the study. In61 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 transcriptand 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 experiencedlonger survival than the patients expressing b2a2 transcript. However, no significant differences wereobserved in the duration of the chronic phase between the two groups. CONCLUSIONS: The type of BCR genebreakpoint seems to have no prognostic value in patients with chronic myeloid leukemia. The longer survivalof patients expressing the b3a2 transcript may be caused by the less aggressive course of the acceleratedor blastic phase.
Keywords: Adolescent, Adult, Aged, DNA Damage, Female, Fusion Proteins, bcr-abl, Genes, abl, Humans, Leukemia, Myeloid, Chronic, Male, Middle Aged, Mutation, Prognosis, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Treatment Outcome