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), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 85:22; ISSN PNASA; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BIOLOGY
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENESIS
CHROMOSOMAL ABERRATIONS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISEASES
DNA SEQUENCING
GENE REGULATION
GENES
GENETICS
HEMIC DISEASES
HYBRIDIZATION
IMMUNE SYSTEM DISEASES
ISOTOPES
LEUKEMIA
LEUKOCYTES
LIGHT NUCLEI
LYMPHOCYTES
MATERIALS
MUTATIONS
NEOPLASMS
NUCLEI
ODD-ODD NUCLEI
ONCOGENES
PATHOGENESIS
PATIENTS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
RADIOISOTOPES
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS
TUMOR CELLS