Evolution of B-cell malignancy; Pre-B-cell leukemia resulting from MYC activation in a B-cell neoplasm with a rearranged BCL2 gene
- Wistar Institute of Anatomy and Biology, Philadelphia, PA (USA)
The authors have analyzed the molecular genetics of the breakpoints involved in the t(8;14) and t(14;18) translocations of an acute pre-B-cell leukemia from a patient with a history of follicular lymphoma. In this patient's leukemic cells, the breakpoint of the t(14;18) translocation occurred in the major breakpoint-cluster region of the BCL2 gene and became linked to the J{sub H}4 joining-region gene segment of the immunoglobulin heavy-chain locus on the 14q+ chromosome as previously observed in follicular lymphoma. An N region and heptamer and nonamer signal sequences indicated that this translocation occurred as a mistake in V{sub H}-D{sub H}-J{sub H} joining (where V{sub H} and D{sub H} are the variable and diversity segments). In the t(8;14) translocation, the breakpoint was located immediately 5' of the first exon of the MYC protooncogene, which was juxtaposed with the C{gamma}2 constant gene segment of the second 14q+ chromosome. The finding of repeated sequences typical of switch regions suggested that this translocation occurred during heavy-chain isotype switching, resulting in progression to pre-B-cell leukemia with both the 5(8;14) and the t(14;18) translocations. The terminal deoxynucleotidyltransferase-positive phenotype of the patient's leukemic cells further suggests that the pre-B-cell leukemia was derived from a pre-B cell carrying a t(14;18) translocation in the original follicular lymphoma. The polymerase chain reaction method was then used to identify cancer cells in the bone marrow of the patient.
- OSTI ID:
- 5546724
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 85:22; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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CARCINOGENESIS
GENETICS
ONCOGENES
GENE REGULATION
TUMOR CELLS
CHROMOSOMAL ABERRATIONS
DNA SEQUENCING
HYBRIDIZATION
LEUKEMIA
LYMPHOCYTES
PATIENTS
PHOSPHORUS 32
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BIOLOGY
BLOOD
BLOOD CELLS
BODY FLUIDS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISEASES
GENES
HEMIC DISEASES
IMMUNE SYSTEM DISEASES
ISOTOPES
LEUKOCYTES
LIGHT NUCLEI
MATERIALS
MUTATIONS
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ODD-ODD NUCLEI
PATHOGENESIS
PHOSPHORUS ISOTOPES
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STRUCTURAL CHEMICAL ANALYSIS
550401* - Genetics- Tracer Techniques