THE BREAKPOINT CLUSTER REGION SITE IN PATIENTS WITH PHILADELPHIA-CHROMOSOME-POSITIVE CHRONIC MYELOGENOUS LEUKEMIA - CLINICAL, LABORATORY, AND PROGNOSTIC CORRELATIONS

Background. The breakpoint site of the breakpoint cluster region (bcr) has been correlated with patient characteristics, with the disease ph ase, and with the prognosis of patients with chronic myelogenous leuke mia (CML), but the findings remain controversial. Methods. Appropriate restriction enzymes and the 3' and universal probes were used to map the breakpoint site by Southern blot analysis into 5' and 3' breakpoin ts and a breakpoint in zone 3 (or fragment 2) in 362 patients in diffe rent phases of CML (238 in early chronic phase, 69 in late chronic pha se, 31 in accelerated phase, and 24 in blastic phase]. Standard statis tical methods were used to evaluate differences in characteristics and in prognosis by the breakpoint site. Results. No correlation was note d between CML phases and breakpoint site. Among patients in the early chronic phase, thrombocytosis was significantly associated with the 3' breakpoint site (P = 0.02], whereas peripheral basophilia occurred mo re frequently with the 5' breakpoint site (P = 0.05). Other patient an d disease characteristics were similar in frequency among the breakpoi nt-site subgroups. There was no difference in response to alpha-interf eron therapy (186 patients treated) by the breakpoint site. Survival, dated from either referral to the authors' institution or from diagnos is, was not significantly different among patients with early chronic phase CML by the breakpoint site. However, patients with a 3' deletion tended to have a shorter survival. Conclusion. Determination of the b reakpoint site by Southern blot analysis does not help to predict prog nosis of patients with CML.