Molecular analysis in chronic granulocytic leukaemia: location of breakpoints within M-BCR and relationship with presentation platelet counts

Summary Rearrangements within the major breakpoint cluster region (M-BCR) were demonstrated by Southern blot analysis for 74 of 80 patients with Philadelphia (Ph1) positive chronic granulocytic leukaemia (CGL) and for one and three patients with Ph1 negative CGL. Multiple restriction enzyme digestion permitted the breakpoint within the M-BCR to be localized relative to the central Hind III site for 71 patients. 62% had 5′ rearrangements and 38% had 3′ rearrangements. Those with 3′ rearrangements had significantly higher platelet counts at presentation than those with 5′ rearrangements (P < 0.001). We examined factors (such as patient selection criteria and retrospective analysis) which may have influenced previous reports of the prognostic value of the breakpoint location within M-BCR. For patients diagnosed after November 1988 (prospective cases), no significant difference was observed for the duration of chronic phase for patients with 5′ or 3′ rearrangements (P= 0.83, Logrank test). We conclude that, although higher presentation platelet counts were associated with 3′ rearrangements, the location of the breakpoint within the M-BCR appears to be of limited prognostic value.