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 c ases have been analysed to determine the breakpoint site and its relat ionship to clinical features, cytogenetic response, duration of chroni c phase and survival. 119 cases have had RNA analysis performed to det ermine the type of BCR/ABL transcript and have also been analysed in a similar way. Presenting features at diagnosis including age, sex, whi te-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 pr esenting white-cell count was <100x10(9)/l, those with b(3)a(2) transc ript did have a significantly higher platelet count. Analysis by Sokal risk grouping showed no difference for 5' or 3' breakpoints but a tre nd for lower stage among those with b(2)a(2) transcripts, No correlati on was found either for genomic breakpoint site or BCR/ABL RNA transcr ipt 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.