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PMID: 2682663 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Activation of MYC in a masked t(8;17) translocation results in an aggressive B-cell leukemia.

Gauwerky CE, Huebner K, Isobe M, Nowell PC, Croce CM

Abstract

We have analyzed the oncogene rearrangements involving BCL2 and MYC in the leukemia cells of a patient with an aggressive prolymphocytic leukemia that had an abnormal karyotype including a t(14;18) translocation and a chromosome 17q+. Molecular analysis showed that BCL2 was rearranged in the major breakpoint cluster region and had joined into the immunoglobulin heavy chain gene as in follicular lymphoma. Cloning and sequence analysis of the rearranged MYC gene revealed that MYC was truncated at the Pvu II site at the end of the first exon of MYC and had joined into the regulatory elements of a gene that we called BCL3 (B-cell leukemia/lymphoma 3). The BCL3 locus was mapped to chromosome 17 band q22. We found BCL3 transcribed as a message of 1.7 kilobases in many hematopoietic cell lines representing all hematopoietic lineages. In the patient's leukemia cells, the truncated MYC gene was highly expressed under the influence of BCL3 regulatory elements, leading to an aggressive B-cell leukemia that presumably had been derived from an indolent lymphoma carrying a rearranged BCL2 gene.

MeSH Terms
Base Sequence Blotting, Northern Chromosomes, Human, Pair 17 Chromosomes, Human, Pair 8 DNA/genetics DNA Probes DNA, Neoplasm/genetics Female Humans Leukemia, B-Cell/genetics Molecular Sequence Data Placenta/analysis Pregnancy Protein-Tyrosine Kinases/genetics Proto-Oncogene Proteins/genetics Proto-Oncogene Proteins c-myc Proto-Oncogenes Regulatory Sequences, Nucleic Acid Restriction Mapping Translocation, Genetic
Chemicals
DNA Probes DNA, Neoplasm Proto-Oncogene Proteins Proto-Oncogene Proteins c-myc DNA Protein-Tyrosine Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Gauwerky C E
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140.
Huebner K
Isobe M
Nowell P C
Croce C M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1989-11-00
Pages
8867-71
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC298391
Subset
IM
Grants
NCI NIH HHS · CA 01279 · United States
NCI NIH HHS · CA 39860 · United States
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