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 phase, and with the prognosis of patients with chronic myelogenous leukemia (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' breakpoints and a breakpoint in zone 3 (or fragment 2) in 362 patients in different phases of CML (238 in early chronic phase, 69 in late chronic phase, 31 in accelerated phase, and 24 in blastic phase). Standard statistical methods were used to evaluate differences in characteristics and in prognosis by the breakpoint site.


RESULTS
No correlation was noted 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 more frequently with the 5' breakpoint site (P = 0.05). Other patient and disease characteristics were similar in frequency among the breakpoint-site subgroups. There was no difference in response to alpha-interferon therapy (186 patients treated) by the breakpoint site. Survival, dated from either referral to the authors' institution or from diagnosis, 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.


CONCLUSIONS
Determination of the breakpoint site by Southern blot analysis does not help to predict prognosis of patients with CML.
Verschraegen
C F
CF
Department of Hematology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Kantarjian
H M
HM
Hirsch-Ginsberg
C
C
Lee
M S
MS
O'Brien
S
S
Rios
M B
MB
Stass
S A
SA
Keating
M
M
Talpaz
M
M
D002892:Chromosomes, Human, Pair 22; D004273:DNA, Neoplasm / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D015183:Restriction Mapping; D016019:Survival Analysis; D014178:Translocation, Genetic
D004273:DNA, Neoplasm; D016898:Interferon-alpha; D016044:Fusion Proteins, bcr-abl