TY - JOUR
T1 - Analysis of breakpoints within the bcr gene and their correlation with the clinical course of Philadelphia-positive chronic myelogenous leukemia
AU - Shtalrid, M.
AU - Talpaz, M.
AU - Kurzrock, R.
AU - Kantarjian, H.
AU - Trujillo, J.
AU - Gutterman, J.
AU - Yoffe, G.
AU - Blick, M.
PY - 1988
Y1 - 1988
N2 - Chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation between chromosomes 9 and 22. The breakpoints on chromosome 22 are clustered within a 5.8-kilobase (kb) DNA fragment known as the breakpoint cluster region (bcr), which encodes part of a functionally active gene. We analyzed the bcr in DNAs from 108 consecutive, unselected Philadelphia chromosome-positive CML patients by Southern blot and determined five restriction enzyme fragments within which breaks occur on chromosome 22. The exact sublocalization was determined in the DNA of 100 patients. It was found to be within the 5.8-kb bcr in 99 patients and outside the bcr in only one. Within the bcr, most of the breakpoints occurred in fragments 1, 2, and 3. Overall, laboratory and clinical features of CML did not correlate with specific breakpoint fragments, but chronic-phase duration was longer in patients with a breakpoint in fragment 2 of the bcr. Large 3' bcr deletions were found in nine patients but did not influence clinical outcome. DNA from one of six patients analyzed both during chronic phase and blastic crisis showed an additional aberrant fragment, which suggested that a second abnormal clone developed in blastic crisis.
AB - Chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation between chromosomes 9 and 22. The breakpoints on chromosome 22 are clustered within a 5.8-kilobase (kb) DNA fragment known as the breakpoint cluster region (bcr), which encodes part of a functionally active gene. We analyzed the bcr in DNAs from 108 consecutive, unselected Philadelphia chromosome-positive CML patients by Southern blot and determined five restriction enzyme fragments within which breaks occur on chromosome 22. The exact sublocalization was determined in the DNA of 100 patients. It was found to be within the 5.8-kb bcr in 99 patients and outside the bcr in only one. Within the bcr, most of the breakpoints occurred in fragments 1, 2, and 3. Overall, laboratory and clinical features of CML did not correlate with specific breakpoint fragments, but chronic-phase duration was longer in patients with a breakpoint in fragment 2 of the bcr. Large 3' bcr deletions were found in nine patients but did not influence clinical outcome. DNA from one of six patients analyzed both during chronic phase and blastic crisis showed an additional aberrant fragment, which suggested that a second abnormal clone developed in blastic crisis.
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U2 - 10.1182/blood.v72.2.485.bloodjournal722485
DO - 10.1182/blood.v72.2.485.bloodjournal722485
M3 - Article
C2 - 3165294
AN - SCOPUS:0023749490
SN - 0006-4971
VL - 72
SP - 485
EP - 490
JO - Blood
JF - Blood
IS - 2
ER -