The position of the M‐BCR breakpoint does not predict the duration of chronic phase or survival in chronic myeloid leukaemia

Abstract

It has been reported that patients with chronic myeloid leukaemia (CML) with 5’breakpoints within the major breakpoint cluster region (M-BCR) of the BCR gene have somewhat better prognoses than those with 3’breakpoints. We studied the position of the breakpoint in 67 patients with CML in chronic phase using conventional Southern blotting. Using restriction enzymes BglII, BamHI and HindIII and two genomic probes, a 0.6 kb (3’M-BCR) probe hybridizing to a part of the intron between exons b3 and b4 and a 2.0 kb (5’M-BCR) probe hybridizing to sequences including exon b1, we localized the breakpoint in M-BCR as occurring 5’(n= 38) or 3’(n= 28) of the HindIII restriction site located just downstream of exon b3. We failed to localize the breakpoint in one patient. The median durations of chronic phase (37 versus 44 months respectively) and of survival (50 versus 51 months respectively) for patients with 5’and 3’breakpoints were not significantly different. When we analysed only patients whose DNA was collected within 4 weeks of diagnosis (5’breakpoints, n= 30; 3’breakpoints, n= 19), there was again no significant difference in duration of chronic phase or survival. The median survivals of patients divided into good, intermediate and poor prognosis categories in accordance with the prognostic index developed by Sokal and colleagues were 54, 50 and 26 months respectively. This study confirms the value of the Sokal prognostic index but provides no support for the notion that the precise genomic position of the breakpoint in M-BCR correlates with prognosis.