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 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.

Immature CD34+CD19− progenitor/stem cells in TEL/AML1-positive acute lymphoblastic leukemia are genetically and functionally normal

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 640-646 ◽  
Author(s):  
Marc Hotfilder ◽  
Silja Röttgers ◽  
Annegret Rosemann ◽  
Heribert Jürgens ◽  
Jochen Harbott ◽  
...  
Keyword(s):  
Stem Cell ◽  
In Situ Hybridization ◽  
Acute Lymphoblastic Leukemia ◽  
Cell Clone ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Cell Fraction ◽  
Rt Pcr

Abstract One important question in stem cell biology of childhood acute lymphoblastic leukemia (ALL) is whether immature CD34+CD19− cells are part of the leukemic cell clone. CD34+CD19− cells from the bone marrow of 9 children with TEL/AML1-positive ALL were purified by flow sorting and subjected to reverse transcriptase–polymerase chain reaction (RT-PCR), fluorescence in situ hybridization, and methylcellulose cultures. In 3 of 8 patients analyzed by RT-PCR, noTEL/AML1-positive cells could be detected in the CD34+CD19− cell fraction. Altogether, the percentage of TEL/AML1-positive cells was low: 1.6% (n = 8; SD 2.2%) by nested real-time RT-PCR and 2.5% (n = 5; SD 2.6%) by fluorescence in situ hybridization. This correlated with the percentage of contaminating CD19+ leukemic cells in the CD34+CD19− cell fraction in 6 control sorts (mean 4.6%, SD 3.6%), indicating that the low levels of leukemic cells detected in the CD34+CD19− cell fraction could be attributed to sorter errors. Methylcellulose cultures in 3 patients provided further evidence that CD34+CD19− cells represent a candidate normal cell population. The clonogenicity of the CD34+CD19− cell fraction was similar to normal progenitors, including growth of primitive granulocyte, erythroid, macrophage, megakaryocyte colony-forming units. Each of 92 colonies from cultures with CD34+CD19− cells tested negative for TEL/AML1. In conclusion, our data support the hypothesis that the leukemia inTEL/AML1-positive childhood ALL originates in a CD19+ lymphoid progenitor. This has many therapeutic implications, eg, for purging of autologous stem cell products, flow cytometric monitoring of minimal residual disease, and targeting immunotherapy against the leukemic cell clone.

scholarly journals Breakpoints at 11q23 in infant leukemias with the t(11;19)(q23;p13) are clustered

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2172-2175 ◽  
Author(s):  
GJ Morgan ◽  
F Cotter ◽  
FE Katz ◽  
SA Ridge ◽  
P Domer ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Blot Analysis ◽  
Genomic Dna ◽  
Southern Blot Analysis ◽  
Yeast Artificial Chromosome ◽  
Lymphoblastic Leukemia ◽  
Restriction Enzymes ◽  
Artificial Chromosome ◽  
Leukemic Cells ◽  
Bamhi Fragment

Abstract We have analyzed a series of nine infant leukemias that carry a t(11;19)(q23;p13). They had the morphologic features of acute lymphoblastic leukemia (ALL) and expressed markers typical of B-cell progenitor ALL or pre-B ALL; one coexpressed myeloid markers in addition to lymphoid markers (biphenotypic). Two probes (P/S4 and 98.40) subcloned from a yeast artificial chromosome (YAC) known to span the breakpoint in the t(4;11) were used to investigate DNA isolated from the leukemic cells of these patients. A total of approximately 15 kb of genomic DNA in the vicinity of the probes was examined by conventional Southern blot analysis using a series of restriction enzymes. In eight of the nine cases, the breakpoint could be mapped to an approximately 10-kb BamHI fragment disclosed by hybridization to the P/S4 probe.

scholarly journals Breakpoints at 11q23 in infant leukemias with the t(11;19)(q23;p13) are clustered

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2172-2175
Author(s):  
GJ Morgan ◽  
F Cotter ◽  
FE Katz ◽  
SA Ridge ◽  
P Domer ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Blot Analysis ◽  
Genomic Dna ◽  
Southern Blot Analysis ◽  
Yeast Artificial Chromosome ◽  
Lymphoblastic Leukemia ◽  
Restriction Enzymes ◽  
Artificial Chromosome ◽  
Leukemic Cells ◽  
Bamhi Fragment

We have analyzed a series of nine infant leukemias that carry a t(11;19)(q23;p13). They had the morphologic features of acute lymphoblastic leukemia (ALL) and expressed markers typical of B-cell progenitor ALL or pre-B ALL; one coexpressed myeloid markers in addition to lymphoid markers (biphenotypic). Two probes (P/S4 and 98.40) subcloned from a yeast artificial chromosome (YAC) known to span the breakpoint in the t(4;11) were used to investigate DNA isolated from the leukemic cells of these patients. A total of approximately 15 kb of genomic DNA in the vicinity of the probes was examined by conventional Southern blot analysis using a series of restriction enzymes. In eight of the nine cases, the breakpoint could be mapped to an approximately 10-kb BamHI fragment disclosed by hybridization to the P/S4 probe.

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