Distribution of breakpoint within the breakpoint cluster region (bcr) in chronic myelogenous leukemia with a complex philadelphia chromosome translocation

1989 ◽  
Vol 32 (3) ◽  
pp. 194-199 ◽  
Author(s):  
Hikari Nishigaki ◽  
Johji Inazawa ◽  
Shinichi Misawa ◽  
Kazuhiro Nishida ◽  
Tsukasa Okuda ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Philadelphia Chromosome ◽  
Chromosome Translocation ◽  
Myelogenous Leukemia ◽  
Breakpoint Cluster Region ◽  
Cluster Region

scholarly journals Duplication of small segments within the major breakpoint cluster region in chronic myelogenous leukemia

Blood ◽  
1993 ◽  
Vol 81 (6) ◽  
pp. 1567-1572 ◽  
Author(s):  
CE Litz ◽  
JS McClure ◽  
CM Copenhaver ◽  
RD Brunning
Keyword(s):  
Small Group ◽  
Chronic Myelogenous Leukemia ◽  
Sequence Data ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Breakpoint Cluster Region ◽  
Cluster Region ◽  
Two Samples ◽  
Chromosome 9Q ◽  
Bamhi Site

The t(9;22) in chronic myelogenous leukemia (CML) may be reciprocal or, in a minority of cases, may result in an extensive deletion of a portion of the major breakpoint cluster region (M-bcr) of the BCR. This report provides evidence of the duplication of small segments within the M-bcr in a small group of patients with CML. Southern blots of Bgl II and Bgl II/BamHI double-digested DNA from the blood or bone marrow of 46 patients with CML were probed with a 5' 1.4-kb Taq I/HindIII M- bcr probe and a 3' 2-kb HindIII/BamHI M-bcr probe. In three patients, rearrangements were noted with both probes in Bgl II-digested DNA, but were not present in Bgl II/BamHI-digested DNA with either probe. Southern analysis of DNA samples double-digested with Bgl II and BspHI from two of these three cases showed no rearrangements with either probe; the M-bcr BspHI site is located 26 bp 3' of the BamHI site in the second intron of the M-bcr. The presence of a rearranged M-bcr with both probes in Bgl II-digested DNA and the lack of rearrangement in Bgl II/BamHI and Bgl II/BspHI double-digested DNA suggest the presence of M- bcr BamHI and BspHI sites on both 9q+ chromosome (9q+) and the Philadelphia chromosome (Ph). This implies a duplication of at least the 26-bp M-bcr BamHI/BspHI fragment in these two samples. Sequence data from one of these two cases confirmed the M-bcr breakpoints to be staggered; the Ph M-bcr breakpoint occurred 258 bp downstream from the 9q+ M-bcr breakpoint. It is concluded that a duplication of small segments within the M-bcr occurs in a small group of patients with CML, which may lead to pseudogermline patterns on Southern blot. Such a duplication may provide insight into the mechanism of some chromosomal translocations in neoplasia.

scholarly journals Duplication of small segments within the major breakpoint cluster region in chronic myelogenous leukemia

Blood ◽  
1993 ◽  
Vol 81 (6) ◽  
pp. 1567-1572 ◽  
Author(s):  
CE Litz ◽  
JS McClure ◽  
CM Copenhaver ◽  
RD Brunning
Keyword(s):  
Small Group ◽  
Chronic Myelogenous Leukemia ◽  
Sequence Data ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Breakpoint Cluster Region ◽  
Cluster Region ◽  
Two Samples ◽  
Chromosome 9Q ◽  
Bamhi Site

Abstract The t(9;22) in chronic myelogenous leukemia (CML) may be reciprocal or, in a minority of cases, may result in an extensive deletion of a portion of the major breakpoint cluster region (M-bcr) of the BCR. This report provides evidence of the duplication of small segments within the M-bcr in a small group of patients with CML. Southern blots of Bgl II and Bgl II/BamHI double-digested DNA from the blood or bone marrow of 46 patients with CML were probed with a 5' 1.4-kb Taq I/HindIII M- bcr probe and a 3' 2-kb HindIII/BamHI M-bcr probe. In three patients, rearrangements were noted with both probes in Bgl II-digested DNA, but were not present in Bgl II/BamHI-digested DNA with either probe. Southern analysis of DNA samples double-digested with Bgl II and BspHI from two of these three cases showed no rearrangements with either probe; the M-bcr BspHI site is located 26 bp 3' of the BamHI site in the second intron of the M-bcr. The presence of a rearranged M-bcr with both probes in Bgl II-digested DNA and the lack of rearrangement in Bgl II/BamHI and Bgl II/BspHI double-digested DNA suggest the presence of M- bcr BamHI and BspHI sites on both 9q+ chromosome (9q+) and the Philadelphia chromosome (Ph). This implies a duplication of at least the 26-bp M-bcr BamHI/BspHI fragment in these two samples. Sequence data from one of these two cases confirmed the M-bcr breakpoints to be staggered; the Ph M-bcr breakpoint occurred 258 bp downstream from the 9q+ M-bcr breakpoint. It is concluded that a duplication of small segments within the M-bcr occurs in a small group of patients with CML, which may lead to pseudogermline patterns on Southern blot. Such a duplication may provide insight into the mechanism of some chromosomal translocations in neoplasia.

Breakpoint cluster region rearrangements in chronic myelogenous leukemia with a masked Philadelphia chromosome

1987 ◽  
Vol 25 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Junko H. Ohyashiki ◽  
Kazuma Ohyashiki ◽  
Alan J. Kinniburgh ◽  
Azra Raza ◽  
Harvey D. Preisler ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Breakpoint Cluster Region ◽  
Cluster Region

Philadelphia-negative chronic myelogenous leukemia with breakpoint cluster region rearrangement: molecular analysis, clinical characteristics, and response to therapy.

1988 ◽  
Vol 6 (10) ◽  
pp. 1569-1575 ◽  
Author(s):  
M Shtalrid ◽  
M Talpaz ◽  
M Blick ◽  
P Romero ◽  
H Kantarjian ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Clinical Features ◽  
Molecular Analysis ◽  
Response To Therapy ◽  
Myelogenous Leukemia ◽  
Chromosome 2 ◽  
Breakpoint Cluster Region ◽  
Cluster Region ◽  
Ifn Alpha ◽  
Alpha Therapy

We have detected rearrangement in the breakpoint cluster region (bcr) on chromosome 22 in cells derived from seven chronic myelogenous leukemia (CML) patients who had no cytogenetic evidence of a chromosome abnormality. These Philadelphia (Ph)-negative, bcr rearrangement-positive CML patients had clinical features and laboratory parameters that bore a strong resemblance to those of Ph-positive CML; all patients have shown a favorable response to hydroxyurea, busulphan, or alpha interferon (IFN-alpha) therapy. In one patient, because of the deletion of distal 3' sequences, detection of bcr rearrangement required a large probe that recognized proximal 5' sequences. Cells obtained from five patients were studied by Northern blotting and showed an aberrant 8 kilobase (kb) mRNA indistinguishable from the bcr-abl transcript that is felt to be a pathogenetic factor in Ph-positive CML. In three patients with a normal karyotype, bcr rearrangement was detected at the time of hematologic remission, and represented the only evidence for persistent malignancy. Our results suggest that: (1) the presence of bcr rearrangement in CML is associated with clinical features of Ph-positive disease, even in the absence of the Ph chromosome; (2) deletions occur within bcr and necessitate the use of probes covering both 5' and 3' DNA segments for accurate diagnosis; (3) molecular analysis may provide a useful approach to the follow-up of leukemia therapy in some patients; and (4) these patients respond to hydroxyurea, busulphan, and IFN-alpha therapy.

scholarly journals Quantification of the breakpoint cluster region rearrangement for clinical monitoring in Philadelphia chromosome-positive chronic myeloid leukemia

Blood ◽  
1995 ◽  
Vol 85 (10) ◽  
pp. 2705-2710 ◽  
Author(s):  
CF Verschraegen ◽  
M Talpaz ◽  
CF Hirsch-Ginsberg ◽  
R Pherwani ◽  
MB Rios ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Philadelphia Chromosome ◽  
Disease Suppression ◽  
Myelogenous Leukemia ◽  
Molecular Response ◽  
Breakpoint Cluster Region ◽  
Cluster Region ◽  
Molecular Studies

The purpose of this report was to evaluate scintigraphy analysis of Southern blot hybridization as a method to quantify the breakpoint cluster region (BCR) rearrangement of Philadelphia chromosome (Ph)+ chronic myelogenous leukemia (CML). Cytogenetic and molecular studies performed simultaneously on 474 bone marrow and/or blood samples from 300 patients treated with alpha-interferon-based therapy were compared. Molecular results were expressed as the percentage of rearranged BCR bands versus the total scintigraphic signal. The percentage of Ph+ metaphases was calculated on 25 metaphases. The results of molecular studies obtained on both peripheral blood and bone marrow samples were identical. The rank correlation between the BCR quantification and the percentage of Ph positivity in 465 samples was excellent (r = .78). However, of 99 samples with a normal karyotype, 24% had a BCR rearrangement. Of 86 samples with no BCR rearrangement, 13% showed a Ph chromosome. Of 49 samples with partial cytogenetic remission (Ph+ metaphases, 1% to 34%), 23% had no BCR rearrangement. In samples with a minor or no cytogenetic response (Ph+ metaphases, > 34%), BCR analysis overestimated the degree of response in 73 of 326 samples (22%). Nevertheless, survival analysis by BCR quantification level showed statistically better outcome for patients in complete or partial molecular response (P < .01). Molecular quantification of BCR was useful in monitoring the course of Ph+ CML. This method, which can be used on peripheral blood, detected residual disease not shown by cytogenetic analysis and was prognostically relevant as a measure of disease suppression.

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