scholarly journals Translocation of oncogene c-sis from chromosome 22 to chromosome 11 in a Ewing sarcoma-derived cell line.

1985 ◽  
Vol 5 (2) ◽  
pp. 427-429 ◽  
Author(s):  
A G van Kessel ◽  
C Turc-Carel ◽  
A de Klein ◽  
G Grosveld ◽  
G Lenoir ◽  
...  
Keyword(s):  
Ewing Sarcoma ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chinese Hamster ◽  
Chromosome 22 ◽  
Chromosome 11 ◽  
Breakpoint Cluster Region ◽  
Cluster Region ◽  
Sarcoma Cells ◽  
Chromosome Breakpoint

Somatic cell hybrids, obtained after fusion of translocation (11;22)-positive Ewing sarcoma cells and Chinese hamster fibroblasts, were assayed for the presence of immunoglobulin C lambda, Philadelphia chromosome breakpoint cluster region, and c-sis oncogene sequences. It was found that c-sis was translocated from chromosome 22 to chromosome 11 in the Ewing sarcoma cells used, indicating that the breakpoint must be proximal to this locus. Moreover, we found that the chromosome 22-linked C lambda and breakpoint cluster region sequences are not translocated. This result confirms an earlier cytogenetic observation that the Ewing sarcoma-associated breakpoint in chromosome 22 is distal to those observed in translocation (8;22)-positive Burkitt lymphoma and in Philadelphia chromosome-positive chronic myeloid leukemia.

Translocation of oncogene c-sis from chromosome 22 to chromosome 11 in a Ewing sarcoma-derived cell line

1985 ◽  
Vol 5 (2) ◽  
pp. 427-429
Author(s):  
A G van Kessel ◽  
C Turc-Carel ◽  
A de Klein ◽  
G Grosveld ◽  
G Lenoir ◽  
...  
Keyword(s):  
Ewing Sarcoma ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chinese Hamster ◽  
Chromosome 22 ◽  
Chromosome 11 ◽  
Breakpoint Cluster Region ◽  
Cluster Region ◽  
Sarcoma Cells ◽  
Chromosome Breakpoint

Somatic cell hybrids, obtained after fusion of translocation (11;22)-positive Ewing sarcoma cells and Chinese hamster fibroblasts, were assayed for the presence of immunoglobulin C lambda, Philadelphia chromosome breakpoint cluster region, and c-sis oncogene sequences. It was found that c-sis was translocated from chromosome 22 to chromosome 11 in the Ewing sarcoma cells used, indicating that the breakpoint must be proximal to this locus. Moreover, we found that the chromosome 22-linked C lambda and breakpoint cluster region sequences are not translocated. This result confirms an earlier cytogenetic observation that the Ewing sarcoma-associated breakpoint in chromosome 22 is distal to those observed in translocation (8;22)-positive Burkitt lymphoma and in Philadelphia chromosome-positive chronic myeloid leukemia.

scholarly journals Paternal origin of the rearranged major breakpoint cluster region in chronic myeloid leukemia

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3445-3448 ◽  
Author(s):  
CE Litz ◽  
CM Copenhaver
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Restriction Site ◽  
Molecular Level ◽  
Philadelphia Chromosome ◽  
Chromosome 22 ◽  
Breakpoint Cluster Region ◽  
Cluster Region ◽  
Cytogenetic Studies ◽  
Restriction Site Polymorphisms

Abstract The Philadelphia chromosome, t(9;22), is present in virtually all cases of chronic myeloid leukemia (CML). It has previously been shown by cytogenetic studies that the rearranged chromosome 22 in patients with CML is exclusively maternal in origin. To address this issue at a molecular level, the major breakpoint cluster region (M-bcr) on chromosome 22 was examined using Southern blot assays and M-bcr Pvu II and Mae II restriction site polymorphisms in three CML patients. In all three cases, the rearranged allele was paternal in origin. These results indicate that the paternally derived M-bcr allele may also be involved in the M-bcr rearrangement.

scholarly journals Paternal origin of the rearranged major breakpoint cluster region in chronic myeloid leukemia

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3445-3448
Author(s):  
CE Litz ◽  
CM Copenhaver
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Restriction Site ◽  
Molecular Level ◽  
Philadelphia Chromosome ◽  
Chromosome 22 ◽  
Breakpoint Cluster Region ◽  
Cluster Region ◽  
Cytogenetic Studies ◽  
Restriction Site Polymorphisms

The Philadelphia chromosome, t(9;22), is present in virtually all cases of chronic myeloid leukemia (CML). It has previously been shown by cytogenetic studies that the rearranged chromosome 22 in patients with CML is exclusively maternal in origin. To address this issue at a molecular level, the major breakpoint cluster region (M-bcr) on chromosome 22 was examined using Southern blot assays and M-bcr Pvu II and Mae II restriction site polymorphisms in three CML patients. In all three cases, the rearranged allele was paternal in origin. These results indicate that the paternally derived M-bcr allele may also be involved in the M-bcr rearrangement.

scholarly journals Aberrant methylation of the major breakpoint cluster region in chronic myeloid leukemia

Blood ◽  
1996 ◽  
Vol 88 (6) ◽  
pp. 2241-2249 ◽  
Author(s):  
CE Litz ◽  
JA Vos ◽  
CM Copenhaver
Keyword(s):  
Sequence Analysis ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Nucleotide Position ◽  
Aberrant Methylation ◽  
Breakpoint Cluster Region ◽  
Cluster Region ◽  
Breakpoint Location

Isolated hypomethylated sites exist in the major breakpoint cluster region (M-bcr) where most Philadelphia chromosome (Ph) breakpoints are located. Twenty of 50 (40%) chronic myeloid leukemia (CML) patients were found to have aberrant hypermethylation of these sites on the rearranged M-bcr when compared with control marrows. The aberrancy correlated strongly with M-bcr breakpoint location; 19 of 20 cases had breakpoints located 5′ of the M-bcr Sca I site, and 28 of 30 cases with normal M-bcr methylation had breakpoints located 3′ of the M-bcr Sca I site. Sequence analysis of the Ph M-bcr breakpoints failed to find an M- bcr nucleotide position that delineated the transition between abnormally and normally methylated cases, indicating that the translocation of a critical M-bcr sequence was not responsible for the methylation abnormality. In 3 of 8 CML patients, cells without the t(9;22) were found to have abnormally methylated, unrearranged M-bcrs. The data indicate that abnormally methylated rearranged M-bcrs are present in CML cases with Ph breakpoints 5′ of the M-bcr Sca I site and that the M-bcr in Ph- cells of patients with CML may also be abnormally methylated.

scholarly journals Rearrangement of the breakpoint cluster region and expression of P210 BCR-ABL in a "masked" Philadelphia chromosome-positive acute myeloid leukemia

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1829-1832 ◽  
Author(s):  
CM Price ◽  
F Rassool ◽  
MK Shivji ◽  
J Gow ◽  
CJ Tew ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Chimeric Gene ◽  
Leukemic Cells ◽  
Breakpoint Cluster Region ◽  
Cluster Region ◽  
Acute Myeloid

Abstract The Philadelphia (Ph) translocation t(9;22)(q34;q11) occurs frequently in chronic myeloid leukemia (CML) but is less common in acute lymphoblastic leukemia (ALL) and rare in acute myeloid leukemia (AML). In most cases of CML and some cases of Ph+ ALL the protooncogene ABL from 9q34 is translocated to the breakpoint cluster region (bcr) of the BCR gene at 22q11 to form a chimeric gene encoding a novel 210-kd protein (P210 BCR-ABL) with enhanced tyrosine kinase activity. In other patients with Ph+ ALL and Ph+ AML, the breakpoint probably occurs in the first intron of the BCR gene; this results in a smaller chimeric gene which encodes a P190 BCR-ABL. We studied a patient with AML (FAB M6) arising de novo who had a “masked” Ph chromosome in association with extensive karyotypic changes. The leukemic cells initially showed rearrangement of the bcr, presence of a hybrid mRNA, and expression of the P210 BCR-ABL. These changes were absent in remission. These results support the concept that the BCR-ABL chimeric gene plays a crucial role in leukemogenesis but suggest that factors other than the position of the breakpoint in the BCR gene determine the lineage of the target cell for malignant transformation.

scholarly journals The correlation of breakpoint cluster region rearrangement and p210 phl/abl expression with morphological analysis of Ph-negative chronic myeloid leukemia and other myeloproliferative diseases

Blood ◽  
1988 ◽  
Vol 71 (2) ◽  
pp. 349-355 ◽  
Author(s):  
LM Wiedemann ◽  
KK Karhi ◽  
MK Shivji ◽  
SI Rayter ◽  
SM Pegram ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Protein Tyrosine Kinase ◽  
Blood Film ◽  
Chromosome 22 ◽  
Molecular Alteration ◽  
Breakpoint Cluster Region ◽  
Cluster Region ◽  
Ph Chromosome ◽  
Atypical Cml

Abstract The chromosome 22 derivative, the Philadelphia (Ph) chromosome, results from a reciprocal translocation t(9;22) (q34;q11) and is associated with chronic myeloid leukemia (CML). The translocation can be identified at the DNA level in Ph-positive CML by using a probe to the breakpoint cluster region (bcr). In addition, as a result of this translocation an abl-related 210-kd protein with protein tyrosine kinase (PTK) activity is produced. We analyzed 28 cases of Ph-negative CML for rearrangement of the chromosome 22 sequences and found that eight of the 28 show rearrangement of the bcr. When 12 of the Ph- negative cases were independently reviewed, five were indistinguishable from Ph-positive CML on the basis of morphology, peripheral blood film and clinical details. These five also showed bcr rearrangement. The other seven were reclassified as six atypical CML (aCML) and one chronic myelomonocytic leukemia (CMML). None of these seven showed bcr rearrangement. In addition 11 cases of bcr- CML were assayed for abl- related PTK, and no detectable activity was present, whereas p210 phl/abl PTK was observed both in Ph-positive (three cases examined) and Ph-negative, bcr + (four cases examined) CML. Therefore, bcr + CML, whether or not the Ph chromosome is cytogenetically apparent, involves a similar molecular alteration and produces the 210-kd protein with enhanced PTK activity. Furthermore, these cases can be distinguished from Ph-negative bcr- CML by careful evaluation of clinical and hematologic data.

scholarly journals The correlation of breakpoint cluster region rearrangement and p210 phl/abl expression with morphological analysis of Ph-negative chronic myeloid leukemia and other myeloproliferative diseases

Blood ◽  
1988 ◽  
Vol 71 (2) ◽  
pp. 349-355
Author(s):  
LM Wiedemann ◽  
KK Karhi ◽  
MK Shivji ◽  
SI Rayter ◽  
SM Pegram ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Protein Tyrosine Kinase ◽  
Blood Film ◽  
Chromosome 22 ◽  
Molecular Alteration ◽  
Breakpoint Cluster Region ◽  
Cluster Region ◽  
Ph Chromosome ◽  
Atypical Cml

The chromosome 22 derivative, the Philadelphia (Ph) chromosome, results from a reciprocal translocation t(9;22) (q34;q11) and is associated with chronic myeloid leukemia (CML). The translocation can be identified at the DNA level in Ph-positive CML by using a probe to the breakpoint cluster region (bcr). In addition, as a result of this translocation an abl-related 210-kd protein with protein tyrosine kinase (PTK) activity is produced. We analyzed 28 cases of Ph-negative CML for rearrangement of the chromosome 22 sequences and found that eight of the 28 show rearrangement of the bcr. When 12 of the Ph- negative cases were independently reviewed, five were indistinguishable from Ph-positive CML on the basis of morphology, peripheral blood film and clinical details. These five also showed bcr rearrangement. The other seven were reclassified as six atypical CML (aCML) and one chronic myelomonocytic leukemia (CMML). None of these seven showed bcr rearrangement. In addition 11 cases of bcr- CML were assayed for abl- related PTK, and no detectable activity was present, whereas p210 phl/abl PTK was observed both in Ph-positive (three cases examined) and Ph-negative, bcr + (four cases examined) CML. Therefore, bcr + CML, whether or not the Ph chromosome is cytogenetically apparent, involves a similar molecular alteration and produces the 210-kd protein with enhanced PTK activity. Furthermore, these cases can be distinguished from Ph-negative bcr- CML by careful evaluation of clinical and hematologic data.

scholarly journals Rearrangement of the breakpoint cluster region and expression of P210 BCR-ABL in a "masked" Philadelphia chromosome-positive acute myeloid leukemia

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1829-1832
Author(s):  
CM Price ◽  
F Rassool ◽  
MK Shivji ◽  
J Gow ◽  
CJ Tew ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Chimeric Gene ◽  
Leukemic Cells ◽  
Breakpoint Cluster Region ◽  
Cluster Region ◽  
Acute Myeloid

The Philadelphia (Ph) translocation t(9;22)(q34;q11) occurs frequently in chronic myeloid leukemia (CML) but is less common in acute lymphoblastic leukemia (ALL) and rare in acute myeloid leukemia (AML). In most cases of CML and some cases of Ph+ ALL the protooncogene ABL from 9q34 is translocated to the breakpoint cluster region (bcr) of the BCR gene at 22q11 to form a chimeric gene encoding a novel 210-kd protein (P210 BCR-ABL) with enhanced tyrosine kinase activity. In other patients with Ph+ ALL and Ph+ AML, the breakpoint probably occurs in the first intron of the BCR gene; this results in a smaller chimeric gene which encodes a P190 BCR-ABL. We studied a patient with AML (FAB M6) arising de novo who had a “masked” Ph chromosome in association with extensive karyotypic changes. The leukemic cells initially showed rearrangement of the bcr, presence of a hybrid mRNA, and expression of the P210 BCR-ABL. These changes were absent in remission. These results support the concept that the BCR-ABL chimeric gene plays a crucial role in leukemogenesis but suggest that factors other than the position of the breakpoint in the BCR gene determine the lineage of the target cell for malignant transformation.

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