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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1997-4-1
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pubmed:databankReference |
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/U22381,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/U22387,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/U22388,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/U22389,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/U22390,
http://linkedlifedata.com/resource/pubmed/xref/GENBANK/U22391
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pubmed:abstractText |
The immunoglobulin (Ig) variable region (V) genes expressed by IgM chronic lymphocytic leukemia (CLL) B cells display little or no somatic mutations. However, preliminary findings have shown that Ig V genes of IgA and IgG CLLs may be somatically mutated, suggesting that isotype-switched CLLs may represent a "subtype" of the disease. To investigate the degree and nature of somatic mutations and the role of antigen (Ag) in the clonal selection and expansion of isotype-switched CLLs, and to determine whether specific oncogene or tumor suppressor gene mutations are associated with isotype-switched CLLs, we analyzed the expressed Ig VH gene, bcl-1 and bcl-2 proto-oncogene, and p53 tumor suppressor gene configurations of 3 IgA-, 1 IgG-, and 1 IgA/ IgG-expressing CLLs. These isotype-switched CLL B cells expressed surface HLA-DR, CD19, CD23, and CD5, and displayed no alterations of the bcl-1 and bcl-2 oncogenes and the p53 tumor-suppressor gene. The cDNA VH-D-JH gene sequence was joined with that of the C alpha gene in the B cells of the three IgA CLLs, and with that of the C gamma gene in the IgG CLL B cells. In the IgA/IgG-coexpressing CLL B cells, identical VH-D-JH cDNA sequences were spliced to either C alpha or C gamma genes. In all five CLLs, the pattern of C mu DNA probe hybridization to the digested genomic DNAs was consistent with deletion of the C mu exon from the rearranged Ig gene locus, suggesting that these CLL B cells had undergone DNA switch recombination. In one IgA CLL, the expressed VH gene was unmutated. In all other class-switched CLLs, the Ig VH segment gene was mutated, but the point mutations were not associated with intraclonal diversification. In one IgA and in the IgA/IgG-coexpressing CLL, the nature and distribution of the mutations were consistent with Ag selection. These findings suggest that IgA- and/or IgG-expressing CLLs represent, in their VH gene structure, transformants of B cells at different stages of ontogeny. They also suggest that Ag may play a role in the clonal selection of some of these isotype-switched leukemic cells, but bcl-1 and bcl-2 oncogene rearrangements and p53 tumor suppressor gene mutation are not associated with the pathogenesis of isotype-switched CLLs.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Mar
|
pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
89
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1732-9
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:9057657-Amino Acid Sequence,
pubmed-meshheading:9057657-Base Sequence,
pubmed-meshheading:9057657-Humans,
pubmed-meshheading:9057657-Immunoglobulin A,
pubmed-meshheading:9057657-Immunoglobulin G,
pubmed-meshheading:9057657-Immunoglobulin Switch Region,
pubmed-meshheading:9057657-Immunoglobulin Variable Region,
pubmed-meshheading:9057657-Leukemia, Lymphocytic, Chronic, B-Cell,
pubmed-meshheading:9057657-Molecular Sequence Data
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pubmed:year |
1997
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pubmed:articleTitle |
Molecular characterization of IgA- and/or IgG-switched chronic lymphocytic leukemia B cells.
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pubmed:affiliation |
Department of Pathology, University Medical School of Pécs, Hungary.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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