scholarly journals bcr Rearrangement without juxtaposition of c-abl in chronic myelocytic leukemia.

1985 ◽  
Vol 162 (6) ◽  
pp. 2175-2179 ◽  
Author(s):  
C R Bartram
Keyword(s):  
Blot Analysis ◽  
Southern Blot Analysis ◽  
Gene Rearrangement ◽  
Northern Blot Analysis ◽  
Philadelphia Chromosome ◽  
Leukemic Cells ◽  
Chronic Myelocytic Leukemia ◽  
Myelocytic Leukemia ◽  
Genomic Recombination

Southern blot analysis detected a bcr gene rearrangement within leukemic cells of a Philadelphia chromosome-negative chronic myelocytic leukemia (CML) patient that led to transcription of a novel 7.3 kb bcr RNA species. Participation of the c-abl oncogene in this genomic recombination could be ruled out by in situ hybridization studies and Northern blot analysis.

scholarly journals bcr rearrangement and translocation of the c-abl oncogene in Philadelphia positive acute lymphoblastic leukemia

Blood ◽  
1986 ◽  
Vol 68 (6) ◽  
pp. 1369-1375 ◽  
Author(s):  
A De Klein ◽  
A Hagemeijer ◽  
CR Bartram ◽  
R Houwen ◽  
L Hoefsloot ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Acute Lymphoblastic Leukemia ◽  
Blot Analysis ◽  
Myeloid Leukemia ◽  
Southern Blot Analysis ◽  
Northern Blot Analysis ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Mrna Transcripts

Abstract The Philadelphia (Ph1) chromosome, the cytogenetic hallmark of chronic myeloid leukemia (CML), has also been detected in a significant number of acute lymphoblastic leukemias (ALL). Using in situ hybridization, we demonstrate that in accordance with observations in CML the Ph1 chromosome in ALL patients is the result of a consistent translocation of the c-abl oncogene to the Ph1 chromosome. Southern blot analysis using bcr probes, however, suggests that Ph1-positive ALL includes heterogeneous leukemic subtypes: six ALL patients showed bcr rearrangements as observed in CML; in three other patients recombination involving 5′ bcr sequences could be demonstrated, but the corresponding translocated 3′ bcr sequences were not detectable. A third group of five patients did not show any bcr rearrangements at all. Northern blot analysis using RNA from three Ph1-positive ALL patients revealed that in the leukemic cells of two patients larger c- abl mRNA transcripts were present, as in CML. In the RNA of one patient without a detectable bcr rearrangement, only the normal c-abl mRNA transcripts are present. The observed heterogeneity in bcr rearrangements of this group of Ph1-positive ALL patients is in contrast with the consistent results obtained in more than 50 Ph1- positive CML patients investigated in chronic and acute states.

scholarly journals bcr rearrangement and translocation of the c-abl oncogene in Philadelphia positive acute lymphoblastic leukemia

Blood ◽  
1986 ◽  
Vol 68 (6) ◽  
pp. 1369-1375 ◽  
Author(s):  
A De Klein ◽  
A Hagemeijer ◽  
CR Bartram ◽  
R Houwen ◽  
L Hoefsloot ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Acute Lymphoblastic Leukemia ◽  
Blot Analysis ◽  
Myeloid Leukemia ◽  
Southern Blot Analysis ◽  
Northern Blot Analysis ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Mrna Transcripts

The Philadelphia (Ph1) chromosome, the cytogenetic hallmark of chronic myeloid leukemia (CML), has also been detected in a significant number of acute lymphoblastic leukemias (ALL). Using in situ hybridization, we demonstrate that in accordance with observations in CML the Ph1 chromosome in ALL patients is the result of a consistent translocation of the c-abl oncogene to the Ph1 chromosome. Southern blot analysis using bcr probes, however, suggests that Ph1-positive ALL includes heterogeneous leukemic subtypes: six ALL patients showed bcr rearrangements as observed in CML; in three other patients recombination involving 5′ bcr sequences could be demonstrated, but the corresponding translocated 3′ bcr sequences were not detectable. A third group of five patients did not show any bcr rearrangements at all. Northern blot analysis using RNA from three Ph1-positive ALL patients revealed that in the leukemic cells of two patients larger c- abl mRNA transcripts were present, as in CML. In the RNA of one patient without a detectable bcr rearrangement, only the normal c-abl mRNA transcripts are present. The observed heterogeneity in bcr rearrangements of this group of Ph1-positive ALL patients is in contrast with the consistent results obtained in more than 50 Ph1- positive CML patients investigated in chronic and acute states.

scholarly journals Localization of the human c-sis oncogene in Ph1-positive and Ph1- negative chronic myelocytic leukemia by in situ hybridization

Blood ◽  
1984 ◽  
Vol 63 (1) ◽  
pp. 223-225 ◽  
Author(s):  
CR Bartram ◽  
A de Klein ◽  
A Hagemeijer ◽  
G Grosveld ◽  
N Heisterkamp ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chromosome Region ◽  
Philadelphia Chromosome ◽  
Active Role ◽  
Chromosome 22 ◽  
Chronic Myelocytic Leukemia ◽  
Metaphase Chromosomes ◽  
Myelocytic Leukemia ◽  
Negative Case

Abstract Oncogenes are a group of evolutionary conserved cellular genes (c-onc) homologous to the transforming genes of oncogenic retroviruses (v-onc). Some of them are localized near the breakpoints of specific chromosomal aberrations occurring in various neoplasms, as for example the Philadelphia translocation, t(9;22)(q34;q11), in chronic myelocytic leukemia (CML). Recently, we localized the human c-abl oncogene to chromosome region 9q34 and demonstrated a translocation of this gene to the Philadelphia chromosome (Ph1,22q-) in various forms of Ph1- positive, but not Ph1-negative, chronic myelocytic leukemia (CML). Another human oncogene, c-sis, is located on chromosome 22 and was recently reported to be transferred to chromosome 9q+ in one CML patient. We have now studied 2 CML patients with classic and variant types of Ph1 translocation, one Ph1-negative case, and a healthy control using in situ hybridization of a c-sis probe to metaphase chromosomes. These studies show that c-sis: (1) is localized to region 22q12.3-q13.1, far away from the breakpoint region 22q11 in CML, (2) segregates with the translocated part of chromosome 22 to different chromosomes in Ph1-positive patients, and (3) remains on chromosome 22 in the Ph1-negative case. Therefore, these data give no support for an active role of the c-sis gene in the generation of CML. Thus, if either of these two oncogenes is involved in the development of Ph1-positive CML, c-abl appears to be the more important one.

scholarly journals Karyotype evolution and multilineage involvement of Philadelphia chromosome-positive clones in blastic transformation of two patients with chronic myelocytic leukemia

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1561-1567
Author(s):  
Y Sato ◽  
K Kitano ◽  
S Tsunoda ◽  
M Yoshida ◽  
E Kajii ◽  
...  
Keyword(s):  
Karyotype Evolution ◽  
Chromosomal Abnormalities ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Leukemic Cells ◽  
Specific Cell ◽  
Chronic Myelocytic Leukemia ◽  
Blastic Transformation ◽  
Myelocytic Leukemia ◽  
Additional Chromosomal Abnormalities

Simultaneous analysis of the cell morphology and karyotypes on single colonies was carried out in two patients with Philadelphia chromosome (Ph1)-positive chronic myelocytic leukemia in blastic transformation in order to clarify the origin of leukemic cells involved. Patient no. 1 was in a typical myeloblastic transformation and patient no. 2 in “basophilic transformation.” Both patients exhibited karyotype evolution in blastic phase (BP), so that we could differentiate BP clones with additional chromosomal abnormalities from chronic phase (CP) clones with only Ph1 among single colonies. The number of single colonies yielding two or more analyzable metaphases was 18 in patient no. 1, and 19 in patient no. 2. Among these colonies, only three in patient no. 1 and none in patient no. 2 were from CP clones and 15 in patient no. 1 and 19 in patient no. 2 were from BP clones. Morphological examination revealed that not only blasts but also mature neutrophils, eosinophils, basophils, macrophages, and erythroblasts were derived from BP clones. These results suggested that (1) BP clones developed at the pluripotent stem cell level, (2) additional chromosomal abnormalities were not restricted to occur in a specific cell line representative in BP; and (3) BP clones, if not all, may retain capacity for maturation and differentiation.

scholarly journals Karyotype evolution and multilineage involvement of Philadelphia chromosome-positive clones in blastic transformation of two patients with chronic myelocytic leukemia

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1561-1567 ◽  
Author(s):  
Y Sato ◽  
K Kitano ◽  
S Tsunoda ◽  
M Yoshida ◽  
E Kajii ◽  
...  
Keyword(s):  
Karyotype Evolution ◽  
Chromosomal Abnormalities ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Leukemic Cells ◽  
Specific Cell ◽  
Chronic Myelocytic Leukemia ◽  
Blastic Transformation ◽  
Myelocytic Leukemia ◽  
Additional Chromosomal Abnormalities

Abstract Simultaneous analysis of the cell morphology and karyotypes on single colonies was carried out in two patients with Philadelphia chromosome (Ph1)-positive chronic myelocytic leukemia in blastic transformation in order to clarify the origin of leukemic cells involved. Patient no. 1 was in a typical myeloblastic transformation and patient no. 2 in “basophilic transformation.” Both patients exhibited karyotype evolution in blastic phase (BP), so that we could differentiate BP clones with additional chromosomal abnormalities from chronic phase (CP) clones with only Ph1 among single colonies. The number of single colonies yielding two or more analyzable metaphases was 18 in patient no. 1, and 19 in patient no. 2. Among these colonies, only three in patient no. 1 and none in patient no. 2 were from CP clones and 15 in patient no. 1 and 19 in patient no. 2 were from BP clones. Morphological examination revealed that not only blasts but also mature neutrophils, eosinophils, basophils, macrophages, and erythroblasts were derived from BP clones. These results suggested that (1) BP clones developed at the pluripotent stem cell level, (2) additional chromosomal abnormalities were not restricted to occur in a specific cell line representative in BP; and (3) BP clones, if not all, may retain capacity for maturation and differentiation.

scholarly journals Localization of the human c-sis oncogene in Ph1-positive and Ph1- negative chronic myelocytic leukemia by in situ hybridization

Blood ◽  
1984 ◽  
Vol 63 (1) ◽  
pp. 223-225 ◽  
Author(s):  
CR Bartram ◽  
A de Klein ◽  
A Hagemeijer ◽  
G Grosveld ◽  
N Heisterkamp ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chromosome Region ◽  
Philadelphia Chromosome ◽  
Active Role ◽  
Chromosome 22 ◽  
Chronic Myelocytic Leukemia ◽  
Metaphase Chromosomes ◽  
Myelocytic Leukemia ◽  
Negative Case

Oncogenes are a group of evolutionary conserved cellular genes (c-onc) homologous to the transforming genes of oncogenic retroviruses (v-onc). Some of them are localized near the breakpoints of specific chromosomal aberrations occurring in various neoplasms, as for example the Philadelphia translocation, t(9;22)(q34;q11), in chronic myelocytic leukemia (CML). Recently, we localized the human c-abl oncogene to chromosome region 9q34 and demonstrated a translocation of this gene to the Philadelphia chromosome (Ph1,22q-) in various forms of Ph1- positive, but not Ph1-negative, chronic myelocytic leukemia (CML). Another human oncogene, c-sis, is located on chromosome 22 and was recently reported to be transferred to chromosome 9q+ in one CML patient. We have now studied 2 CML patients with classic and variant types of Ph1 translocation, one Ph1-negative case, and a healthy control using in situ hybridization of a c-sis probe to metaphase chromosomes. These studies show that c-sis: (1) is localized to region 22q12.3-q13.1, far away from the breakpoint region 22q11 in CML, (2) segregates with the translocated part of chromosome 22 to different chromosomes in Ph1-positive patients, and (3) remains on chromosome 22 in the Ph1-negative case. Therefore, these data give no support for an active role of the c-sis gene in the generation of CML. Thus, if either of these two oncogenes is involved in the development of Ph1-positive CML, c-abl appears to be the more important one.

Sign in / Sign up

Export Citation Format

Share Document