scholarly journals A 76-kb duplicon maps close to the BCR gene on chromosome 22 and the ABL gene on chromosome 9: Possible involvement in the genesis of the Philadelphia chromosome translocation

2002 ◽  
Vol 99 (15) ◽  
pp. 9882-9887 ◽  
Author(s):  
G. Saglio ◽  
C. T. Storlazzi ◽  
E. Giugliano ◽  
C. Surace ◽  
L. Anelli ◽  
...  
Keyword(s):  
Philadelphia Chromosome ◽  
Chromosome Translocation ◽  
Chromosome 9 ◽  
Chromosome 22

scholarly journals Variable breakpoints on the Philadelphia chromosome in chronic myelogenous leukemia

Blood ◽  
1985 ◽  
Vol 66 (1) ◽  
pp. 243-245 ◽  
Author(s):  
D Leibowitz ◽  
K Schaefer-Rego ◽  
DW Popenoe ◽  
JG Mears ◽  
A Bank
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Southern Blotting ◽  
Philadelphia Chromosome ◽  
Dna Probes ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Chromosome 22 ◽  
Human Dna ◽  
Translocation Breakpoints ◽  
The Creation

Abstract The abl oncogene is translocated from chromosome 9 to 22 in the creation of the Philadelphia (Ph1) chromosome. This article describes new translocation breakpoints identified in two patients with chronic myelogenous leukemia using Southern blotting and cloned human DNA probes from chromosome 9. The translocation breakpoints on chromosome 9 in both of these patients lie closer to the human cellular abl (c-abl) gene, and the chromosome 22 breakpoints are distributed more widely than previously reported. These data help to define more clearly the chromosomal span of the breakpoints and indicate that some translocations include very little chromosome 9 sequence located 5′ to the c-abl gene.

scholarly journals C-sis and C-abl expression in chronic myelogenous leukemia and other hematologic malignancies

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 839-841
Author(s):  
P Romero ◽  
M Blick ◽  
M Talpaz ◽  
E Murphy ◽  
J Hester ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Chromosomal Rearrangements ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Hematologic Malignancies ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Chromosome 22 ◽  
Aberrant Expression

Cellular oncogenes have been localized at the breakpoints of characteristic chromosomal rearrangements occurring in certain hematologic malignancies. This has been reported to result in aberrant expression of the involved oncogenes. Over 90% of chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation that brings c-abl from chromosome 9 to chromosome 22, and c-sis from chromosome 22 to chromosome 9. To investigate the possible role of these two oncogenes in the leukemic process, we studied their expression in a number of fresh samples obtained from patients with various forms of leukemia, by Northern blot analysis using c-onc probes. Seven of 24 samples obtained from patients with either CML or chronic myelomonocytic leukemia expressed a normal 4.0-kilobase (kb) c- sis transcript. C-sis expression was found only in the accelerated/blast phases but not in the chronic phase of CML. All of the CML Philadelphia chromosome-positive (Ph1+) samples expressed an aberrant 8-kb c-abl transcript. The expression of c-sis in

scholarly journals A coiled-coil oligomerization domain of Bcr is essential for the transforming function of Bcr-Abl oncoproteins.

1993 ◽  
Vol 13 (12) ◽  
pp. 7587-7595 ◽  
Author(s):  
J R McWhirter ◽  
D L Galasso ◽  
J Y Wang
Keyword(s):  
Amino Acids ◽  
Tyrosine Kinase ◽  
Insertional Mutagenesis ◽  
Philadelphia Chromosome ◽  
Coiled Coil ◽  
Lymphoid Cells ◽  
Chromosome 9 ◽  
Actin Binding ◽  
Chromosome 22 ◽  
Oligomerization Domain

In Philadelphia chromosome-positive human leukemias, the c-abl proto-oncogene on chromosome 9 becomes fused to the bcr gene on chromosome 22, and chimeric Bcr-Abl proteins are produced. The fused Bcr sequences activate the tyrosine kinase, actin-binding, and transforming functions of Abl. Activation of the Abl transforming function has been shown to require two distinct domains of Bcr: domain 1 (Bcr amino acids 1 to 63) and domain 2 (Bcr amino acids 176 to 242). The amino acid sequence of domain 1 indicates that it may be a coiled-coil oligomerization domain. We show here that domain 1 of Bcr forms a homotetramer. Tetramerization of Bcr-Abl through Bcr domain 1 correlates with activation of the tyrosine kinase and F-actin-binding functions of Abl. Disruption of the coiled coil by insertional mutagenesis inactivates the oligomerization function as well as the ability of Bcr-Abl to transform Rat-1 fibroblasts or to abrogate interleukin-3 dependence in lymphoid cells. These results strongly suggest that Bcr-Abl oligomers are the active entities in transformation.

scholarly journals C-sis and C-abl expression in chronic myelogenous leukemia and other hematologic malignancies

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 839-841 ◽  
Author(s):  
P Romero ◽  
M Blick ◽  
M Talpaz ◽  
E Murphy ◽  
J Hester ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Chromosomal Rearrangements ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Hematologic Malignancies ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Chromosome 22 ◽  
Aberrant Expression

Abstract Cellular oncogenes have been localized at the breakpoints of characteristic chromosomal rearrangements occurring in certain hematologic malignancies. This has been reported to result in aberrant expression of the involved oncogenes. Over 90% of chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation that brings c-abl from chromosome 9 to chromosome 22, and c-sis from chromosome 22 to chromosome 9. To investigate the possible role of these two oncogenes in the leukemic process, we studied their expression in a number of fresh samples obtained from patients with various forms of leukemia, by Northern blot analysis using c-onc probes. Seven of 24 samples obtained from patients with either CML or chronic myelomonocytic leukemia expressed a normal 4.0-kilobase (kb) c- sis transcript. C-sis expression was found only in the accelerated/blast phases but not in the chronic phase of CML. All of the CML Philadelphia chromosome-positive (Ph1+) samples expressed an aberrant 8-kb c-abl transcript. The expression of c-sis in

scholarly journals Long-range mapping of the Philadelphia chromosome by pulsed-field gel electrophoresis

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 697-702
Author(s):  
CA Westbrook ◽  
CM Rubin ◽  
JJ Carrino ◽  
MM Le Beau ◽  
A Bernards ◽  
...  
Keyword(s):  
Gel Electrophoresis ◽  
Large Scale ◽  
Fusion Gene ◽  
Philadelphia Chromosome ◽  
Pulsed Field Gel Electrophoresis ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Chromosome 22 ◽  
Pulsed Field ◽  
Translocation Breakpoints

The Philadelphia chromosome (Ph1) of chronic myelogenous leukemia (CML) contains sequences from chromosome 9, including the ABL protooncogene, that have been translocated to the breakpoint cluster region (bcr) of chromosome 22, giving rise to a bcr-ABL fusion gene, whose product has been implicated in the genesis of CML. Although chromosome 22 translocation breakpoints in CML virtually always occur within the 5.8- kilobase (kb) bcr, chromosome 9 breakpoints have been identified within the known limits of ABL in only a few instances. For a better understanding of the variability of the breakpoints on chromosome 9, we studied the CML cell line BV173. Using pulsed-field gel electrophoresis (PFGE), large-scale maps of the t(9;22) junctions were constructed. The chromosome 9 breakpoint was shown to have occurred within an ABL intron, 160 kb upstream of the v-abl homologous sequences, but still 35 kb downstream of the 5′-most ABL exon. bcr-ABL and ABL-bcr fusion genes were demonstrated on the Ph1 and the 9q+ chromosomes, respectively; both of these genes are expressed. These results suggest that the 9;22 translocation breakpoints in CML consistently occur within the limits of the large ABL gene. RNA splicing, sometimes of very large regions, appears to compensate for the variability in breakpoint location. These studies show that PFGE is a powerful new tool for the analysis of chromosomal translocations in human malignancies.

A coiled-coil oligomerization domain of Bcr is essential for the transforming function of Bcr-Abl oncoproteins

1993 ◽  
Vol 13 (12) ◽  
pp. 7587-7595
Author(s):  
J R McWhirter ◽  
D L Galasso ◽  
J Y Wang
Keyword(s):  
Amino Acids ◽  
Tyrosine Kinase ◽  
Insertional Mutagenesis ◽  
Philadelphia Chromosome ◽  
Coiled Coil ◽  
Lymphoid Cells ◽  
Chromosome 9 ◽  
Actin Binding ◽  
Chromosome 22 ◽  
Oligomerization Domain

In Philadelphia chromosome-positive human leukemias, the c-abl proto-oncogene on chromosome 9 becomes fused to the bcr gene on chromosome 22, and chimeric Bcr-Abl proteins are produced. The fused Bcr sequences activate the tyrosine kinase, actin-binding, and transforming functions of Abl. Activation of the Abl transforming function has been shown to require two distinct domains of Bcr: domain 1 (Bcr amino acids 1 to 63) and domain 2 (Bcr amino acids 176 to 242). The amino acid sequence of domain 1 indicates that it may be a coiled-coil oligomerization domain. We show here that domain 1 of Bcr forms a homotetramer. Tetramerization of Bcr-Abl through Bcr domain 1 correlates with activation of the tyrosine kinase and F-actin-binding functions of Abl. Disruption of the coiled coil by insertional mutagenesis inactivates the oligomerization function as well as the ability of Bcr-Abl to transform Rat-1 fibroblasts or to abrogate interleukin-3 dependence in lymphoid cells. These results strongly suggest that Bcr-Abl oligomers are the active entities in transformation.

scholarly journals Variable breakpoints on the Philadelphia chromosome in chronic myelogenous leukemia

Blood ◽  
1985 ◽  
Vol 66 (1) ◽  
pp. 243-245
Author(s):  
D Leibowitz ◽  
K Schaefer-Rego ◽  
DW Popenoe ◽  
JG Mears ◽  
A Bank
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Southern Blotting ◽  
Philadelphia Chromosome ◽  
Dna Probes ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Chromosome 22 ◽  
Human Dna ◽  
Translocation Breakpoints ◽  
The Creation

The abl oncogene is translocated from chromosome 9 to 22 in the creation of the Philadelphia (Ph1) chromosome. This article describes new translocation breakpoints identified in two patients with chronic myelogenous leukemia using Southern blotting and cloned human DNA probes from chromosome 9. The translocation breakpoints on chromosome 9 in both of these patients lie closer to the human cellular abl (c-abl) gene, and the chromosome 22 breakpoints are distributed more widely than previously reported. These data help to define more clearly the chromosomal span of the breakpoints and indicate that some translocations include very little chromosome 9 sequence located 5′ to the c-abl gene.

scholarly journals Long-range mapping of the Philadelphia chromosome by pulsed-field gel electrophoresis

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 697-702 ◽  
Author(s):  
CA Westbrook ◽  
CM Rubin ◽  
JJ Carrino ◽  
MM Le Beau ◽  
A Bernards ◽  
...  
Keyword(s):  
Gel Electrophoresis ◽  
Large Scale ◽  
Fusion Gene ◽  
Philadelphia Chromosome ◽  
Pulsed Field Gel Electrophoresis ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Chromosome 22 ◽  
Pulsed Field ◽  
Translocation Breakpoints

Abstract The Philadelphia chromosome (Ph1) of chronic myelogenous leukemia (CML) contains sequences from chromosome 9, including the ABL protooncogene, that have been translocated to the breakpoint cluster region (bcr) of chromosome 22, giving rise to a bcr-ABL fusion gene, whose product has been implicated in the genesis of CML. Although chromosome 22 translocation breakpoints in CML virtually always occur within the 5.8- kilobase (kb) bcr, chromosome 9 breakpoints have been identified within the known limits of ABL in only a few instances. For a better understanding of the variability of the breakpoints on chromosome 9, we studied the CML cell line BV173. Using pulsed-field gel electrophoresis (PFGE), large-scale maps of the t(9;22) junctions were constructed. The chromosome 9 breakpoint was shown to have occurred within an ABL intron, 160 kb upstream of the v-abl homologous sequences, but still 35 kb downstream of the 5′-most ABL exon. bcr-ABL and ABL-bcr fusion genes were demonstrated on the Ph1 and the 9q+ chromosomes, respectively; both of these genes are expressed. These results suggest that the 9;22 translocation breakpoints in CML consistently occur within the limits of the large ABL gene. RNA splicing, sometimes of very large regions, appears to compensate for the variability in breakpoint location. These studies show that PFGE is a powerful new tool for the analysis of chromosomal translocations in human malignancies.

A Unique, Complex Variant Philadelphia Chromosome Translocation in a Patient With Typical Chronic Myelogenous Leukemia

2001 ◽  
Vol 125 (3) ◽  
pp. 437-439
Author(s):  
Raida Oudat ◽  
Zebunnisa Khan ◽  
Armand B. Glassman
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Chromosomal Abnormalities ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Chromosome Translocation ◽  
Chromosome 9 ◽  
Myelogenous Leukemia ◽  
Chromosome 11 ◽  
Ph Chromosome ◽  
Conventional Cytogenetics

Abstract The Philadelphia (Ph) chromosome [der(22) t(9;22)(q34;q11)] is the characteristic chromosomal abnormality found in chronic myelogenous leukemia (CML). This chromosome has been reported in patients with other chromosomal abnormalities. In this study, we describe a patient with hematologically typical chronic-phase CML with an unusual and complex translocation involving chromosomes 9, 11, and 22. These complex translocations were identified by G-banded conventional cytogenetics and confirmed by fluorescence in situ hybridization (FISH) using whole chromosome painting probes (wcp). To the best of our knowledge, these are unique translocations involving the short and the long arms of chromosome 9 in 4 different translocations with the short arm of chromosome 11 and the long arm of chromosome 22.

scholarly journals Significance of bcr-abl molecular detection in chronic myeloid leukemia patients

JMS SKIMS ◽  
2016 ◽  
Vol 19 (2) ◽  
pp. 95-96
Author(s):  
Manzoor A Malik
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Molecular Detection ◽  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Chromosome 9 ◽  
Chromosome 1 ◽  
Chromosome 22 ◽  
Myeloproliferative Disease ◽  
Region Gene

Important advances in the understanding of the molecular basis of chronic myeloid leukemia have resulted in the development of new therapies and changed the paradigm for managing this myeloproliferative disease. The reciprocal translocation of the abl (Abelson murine leukemia) proto-oncogene on chromosome 9 to the bcr (breakpoint cluster region) gene on chromosome 22 creates a transcriptionally active, chimeric bcr-abl gene and gives rise to the Philadelphia chromosome. 1 The genetic hallmark of chronic myeloid leukemia (CML) is the Philadelphia chromosome (Ph), which occurs in at least 95% of CML cases as well as some cases of acute lymphocytic leukemia (ALL; approximately 5% for children, 20% for adults). It also has been reported in some other hematologic disorders, albeit rarely. 2-4  JMS 2016; 19(2):95-96 

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