ANALYSIS OF MOLECULAR BREAKPOINT AND M-RNA TRANSCRIPTS IN A PROSPECTIVE RANDOMIZED TRIAL OF INTERFERON IN CHRONIC MYELOID-LEUKEMIA - NO CORRELATION WITH CLINICAL-FEATURES, CYTOGENETIC RESPONSE, DURATION OF CHRONIC PHASE, OR SURVIVAL

Two hundred and nineteen cases of Ph+ve CML and 15 Ph-ve, BCR+ve CML cases have been analysed to determine the breakpoint site and its relationship to clinical features, cytogenetic response, duration of chronic phase and survival. 119 cases have had RNA analysis performed to determine the type of BCR/ABL transcript and have also been analysed in a similar way. Presenting features at diagnosis including age, sex, white-cell count and platelet count showed no significant difference for those with 5' and 3' breakpoints and those with either b(2)a(2) or b(3)a(2) BCR/ABL transcripts. However, in a subgroup of patients whose presenting white-cell count was <100x10(9)/l, those with b(3)a(2) transcript did have a significantly higher platelet count. Analysis by Sokal risk grouping showed no difference for 5' or 3' breakpoints but a trend for lower stage among those with b(2)a(2) transcripts, No correlation was found either for genomic breakpoint site or BCR/ABL RNA transcript in terms of duration of chronic phase or survival. When stratified by randomized therapy, either interferon-cr or standard chemotherapy, no difference was noted in relation to genomic breakpoint site or BCR/ABL transcript. Cytogenetic response was not related to the molecular findings.