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 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 Analysis of breakpoints within the bcr gene and their correlation with the clinical course of Philadelphia-positive chronic myelogenous leukemia

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 485-490 ◽  
Author(s):  
M Shtalrid ◽  
M Talpaz ◽  
R Kurzrock ◽  
H Kantarjian ◽  
J Trujillo ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Chronic Myelogenous Leukemia ◽  
Clinical Course ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Chromosome 22 ◽  
Blastic Crisis ◽  
Phase Duration ◽  
Dna Fragment

Abstract 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 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.

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 Analysis of breakpoints within the bcr gene and their correlation with the clinical course of Philadelphia-positive chronic myelogenous leukemia

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 485-490
Author(s):  
M Shtalrid ◽  
M Talpaz ◽  
R Kurzrock ◽  
H Kantarjian ◽  
J Trujillo ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Chronic Myelogenous Leukemia ◽  
Clinical Course ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Chromosome 22 ◽  
Blastic Crisis ◽  
Phase Duration ◽  
Dna Fragment

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 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.

scholarly journals New type of Bcr/Abl junction in Philadelphia chromosome-positive chronic myelogenous leukemia

Blood ◽  
1990 ◽  
Vol 76 (9) ◽  
pp. 1819-1824 ◽  
Author(s):  
G Saglio ◽  
A Guerrasio ◽  
C Rosso ◽  
A Zaccaria ◽  
A Tassinari ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Hematologic Malignancies ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Base Pairs ◽  
Rare Type ◽  
Exon 2 ◽  
New Type

Abstract A new and rare type of Bcr/Abl junction between exon C3 of the 3′ portion of the Bcr gene and Abl exon 2 has been identified in the leukemic cells of two Ph1-positive chronic myelogenous leukemia patients in chronic phase. This is the fourth type of Bcr/Abl junction so far identified in Ph1-positive hematologic malignancies and is a consequence of an unusual breakpoint position on chromosome 22 that falls approximately 20 kb downstream of the major breakpoint cluster region (bcr) of the Bcr gene. The new hybrid mRNA is 540 base pairs (bp) longer than that expressed by the K562 cell line and could codify for a Bcr/Abl protein carrying 180 additional aminoacids with respect to the larger P210 protein so far identified. The hematologic phenotype expressed by the two patients carrying this unusual type of Bcr/Abl rearrangement does not significantly differ from that commonly seen in chronic myelogenous leukemia.

scholarly journals New type of Bcr/Abl junction in Philadelphia chromosome-positive chronic myelogenous leukemia

Blood ◽  
1990 ◽  
Vol 76 (9) ◽  
pp. 1819-1824 ◽  
Author(s):  
G Saglio ◽  
A Guerrasio ◽  
C Rosso ◽  
A Zaccaria ◽  
A Tassinari ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Hematologic Malignancies ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Base Pairs ◽  
Rare Type ◽  
Exon 2 ◽  
New Type

A new and rare type of Bcr/Abl junction between exon C3 of the 3′ portion of the Bcr gene and Abl exon 2 has been identified in the leukemic cells of two Ph1-positive chronic myelogenous leukemia patients in chronic phase. This is the fourth type of Bcr/Abl junction so far identified in Ph1-positive hematologic malignancies and is a consequence of an unusual breakpoint position on chromosome 22 that falls approximately 20 kb downstream of the major breakpoint cluster region (bcr) of the Bcr gene. The new hybrid mRNA is 540 base pairs (bp) longer than that expressed by the K562 cell line and could codify for a Bcr/Abl protein carrying 180 additional aminoacids with respect to the larger P210 protein so far identified. The hematologic phenotype expressed by the two patients carrying this unusual type of Bcr/Abl rearrangement does not significantly differ from that commonly seen in chronic myelogenous leukemia.

Variability of the molecular defects corresponding to the presence of a Philadelphia chromosome in human hematologic malignancies

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1203-1208 ◽  
Author(s):  
G Saglio ◽  
A Guerrasio ◽  
A Tassinari ◽  
C Ponzetto ◽  
A Zaccaria ◽  
...  
Keyword(s):  
Blast Crisis ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Hematologic Malignancies ◽  
Myelogenous Leukemia ◽  
Chromosome 22 ◽  
Molecular Defect ◽  
Acute Leukemias ◽  
Precise Position ◽  
Ph Chromosome

By analyzing a total of 107 patients affected by chronic myelogenous leukemia (CML; chronic and blast crisis) or lymphoid and myeloid Philadelphia chromosome (Ph′) positive acute leukemias, we have investigated the relationship between the molecular defect on the Ph′ chromosome and the associated hematologic phenotype. As expected, approximately half of the Ph′ positive acute leukemias showed a breakpoint on chromosome 22 falling outside the “breakpoint cluster region” (bcr) known to be involved in CML. Surprisingly, seven of 80 CML cases in chronic phase also showed rearrangements falling outside the bcr region. In two of these cases the breakpoint on chromosome 22 was mapped between 9 and 12 kb upstream to the bcr region. In another case, the breakpoint was located approximately 16 kb downstream to bcr. In the remaining four cases, the precise position of the rearrangement could not be localized with the available bcr probes. DNAs from patients with CML blast crises showed classical bcr rearrangements. No molecular changes were observed during the progression of the disease in six patients whose DNA from both a chronic and acute phase was available. Our results seem to indicate a greater degree of variability of chromosome 22 breakpoints in CML than previously observed, and the lack of additional rearrangements on the Ph′ chromosome in CML blast crises with respect to chronic phase.

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 Variability of the molecular defects corresponding to the presence of a Philadelphia chromosome in human hematologic malignancies

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1203-1208 ◽  
Author(s):  
G Saglio ◽  
A Guerrasio ◽  
A Tassinari ◽  
C Ponzetto ◽  
A Zaccaria ◽  
...  
Keyword(s):  
Blast Crisis ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Hematologic Malignancies ◽  
Myelogenous Leukemia ◽  
Chromosome 22 ◽  
Molecular Defect ◽  
Acute Leukemias ◽  
Precise Position ◽  
Ph Chromosome

Abstract By analyzing a total of 107 patients affected by chronic myelogenous leukemia (CML; chronic and blast crisis) or lymphoid and myeloid Philadelphia chromosome (Ph′) positive acute leukemias, we have investigated the relationship between the molecular defect on the Ph′ chromosome and the associated hematologic phenotype. As expected, approximately half of the Ph′ positive acute leukemias showed a breakpoint on chromosome 22 falling outside the “breakpoint cluster region” (bcr) known to be involved in CML. Surprisingly, seven of 80 CML cases in chronic phase also showed rearrangements falling outside the bcr region. In two of these cases the breakpoint on chromosome 22 was mapped between 9 and 12 kb upstream to the bcr region. In another case, the breakpoint was located approximately 16 kb downstream to bcr. In the remaining four cases, the precise position of the rearrangement could not be localized with the available bcr probes. DNAs from patients with CML blast crises showed classical bcr rearrangements. No molecular changes were observed during the progression of the disease in six patients whose DNA from both a chronic and acute phase was available. Our results seem to indicate a greater degree of variability of chromosome 22 breakpoints in CML than previously observed, and the lack of additional rearrangements on the Ph′ chromosome in CML blast crises with respect to chronic phase.

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.

Sign in / Sign up

Export Citation Format

Share Document