Mutational Status of IgVH Genes Consistent with Antigen-Driven Selection but Not Percent of Mutations Has Prognostic Impact in B-Cell Chronic Lymphocytic Leukemia
Mutational status of immunoglobulin heavy-chain variable-region (IgVH) genes, along with CD38 expression, is a prognostic marker in B-cell chronic lymphocytic leukemia (B-CLL). Configuration of IgVH genes displaying > 2% mismatch has been shown to correlate with longer survivals. In a series of 6...
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| Veröffentlicht in: | Clinical lymphoma 2004-09, Vol.5 (2), p.123-126 |
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| creator | Degan, Massimo Rupolo, Maurizio Dal Bo, Michele Stefanon, Anna Bomben, Riccardo Zucchetto, Antonella Canton, Enrica Berretta, Massimiliano Nanni, Paola Steffan, Agostino Ferruccio Ballerini, Pier Damiani, Daniela Pucillo, Carlo Attadia, Vincenza Colombatti, Alfonso Gattei, Valter |
| description | Mutational status of immunoglobulin heavy-chain variable-region (IgVH) genes, along with CD38 expression, is a prognostic marker in B-cell chronic lymphocytic leukemia (B-CLL). Configuration of IgVH genes displaying > 2% mismatch has been shown to correlate with longer survivals. In a series of 64 B-CLLs, we failed to confirm the prognostic value of the IgVH gene mutational status by using the suggested cutoff. However, the IgVH mutational status maintained its prognostic value only when evidence of antigen-driven selection could be documented. This was accomplished by applying statistical methods aimed at evaluating a significant skewing of replacement mutations from framework to complementary determining regions, as it occurs during germinal center differentiation of B cells. These data caution against wide application of the 2% somatic mutation cutoff as a prognostic determinant without demonstration of antigen-driven selection. |
| doi_str_mv | 10.3816/CLM.2004.n.019 |
| format | Article |
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Configuration of IgVH genes displaying > 2% mismatch has been shown to correlate with longer survivals. In a series of 64 B-CLLs, we failed to confirm the prognostic value of the IgVH gene mutational status by using the suggested cutoff. However, the IgVH mutational status maintained its prognostic value only when evidence of antigen-driven selection could be documented. This was accomplished by applying statistical methods aimed at evaluating a significant skewing of replacement mutations from framework to complementary determining regions, as it occurs during germinal center differentiation of B cells. These data caution against wide application of the 2% somatic mutation cutoff as a prognostic determinant without demonstration of antigen-driven selection.</description><identifier>ISSN: 1526-9655</identifier><identifier>EISSN: 2331-4486</identifier><identifier>DOI: 10.3816/CLM.2004.n.019</identifier><identifier>PMID: 15453928</identifier><language>eng</language><publisher>United States</publisher><subject>ADP-ribosyl Cyclase - genetics ; ADP-ribosyl Cyclase 1 ; Adult ; Aged ; Aged, 80 and over ; Antigens - chemistry ; Antigens, CD - genetics ; CD38 expression ; Cell Differentiation ; Complementary determining regions ; DNA Mutational Analysis ; Female ; Genes, Immunoglobulin - genetics ; Germinal center differentiation ; Humans ; Immunoglobulin Variable Region - genetics ; Leukemia, Lymphocytic, Chronic, B-Cell - genetics ; Male ; Membrane Glycoproteins ; Middle Aged ; Mutation ; Prognosis ; Time Factors</subject><ispartof>Clinical lymphoma, 2004-09, Vol.5 (2), p.123-126</ispartof><rights>2004 Elsevier Inc.</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c340t-c4614eb79395b867709fca85ec25df714ea0753f082f121d3cc49c011ff03593</citedby><cites>FETCH-LOGICAL-c340t-c4614eb79395b867709fca85ec25df714ea0753f082f121d3cc49c011ff03593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15453928$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Degan, Massimo</creatorcontrib><creatorcontrib>Rupolo, Maurizio</creatorcontrib><creatorcontrib>Dal Bo, Michele</creatorcontrib><creatorcontrib>Stefanon, Anna</creatorcontrib><creatorcontrib>Bomben, Riccardo</creatorcontrib><creatorcontrib>Zucchetto, Antonella</creatorcontrib><creatorcontrib>Canton, Enrica</creatorcontrib><creatorcontrib>Berretta, Massimiliano</creatorcontrib><creatorcontrib>Nanni, Paola</creatorcontrib><creatorcontrib>Steffan, Agostino</creatorcontrib><creatorcontrib>Ferruccio Ballerini, Pier</creatorcontrib><creatorcontrib>Damiani, Daniela</creatorcontrib><creatorcontrib>Pucillo, Carlo</creatorcontrib><creatorcontrib>Attadia, Vincenza</creatorcontrib><creatorcontrib>Colombatti, Alfonso</creatorcontrib><creatorcontrib>Gattei, Valter</creatorcontrib><title>Mutational Status of IgVH Genes Consistent with Antigen-Driven Selection but Not Percent of Mutations Has Prognostic Impact in B-Cell Chronic Lymphocytic Leukemia</title><title>Clinical lymphoma</title><addtitle>Clin Lymphoma</addtitle><description>Mutational status of immunoglobulin heavy-chain variable-region (IgVH) genes, along with CD38 expression, is a prognostic marker in B-cell chronic lymphocytic leukemia (B-CLL). Configuration of IgVH genes displaying > 2% mismatch has been shown to correlate with longer survivals. In a series of 64 B-CLLs, we failed to confirm the prognostic value of the IgVH gene mutational status by using the suggested cutoff. However, the IgVH mutational status maintained its prognostic value only when evidence of antigen-driven selection could be documented. This was accomplished by applying statistical methods aimed at evaluating a significant skewing of replacement mutations from framework to complementary determining regions, as it occurs during germinal center differentiation of B cells. These data caution against wide application of the 2% somatic mutation cutoff as a prognostic determinant without demonstration of antigen-driven selection.</description><subject>ADP-ribosyl Cyclase - genetics</subject><subject>ADP-ribosyl Cyclase 1</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antigens - chemistry</subject><subject>Antigens, CD - genetics</subject><subject>CD38 expression</subject><subject>Cell Differentiation</subject><subject>Complementary determining regions</subject><subject>DNA Mutational Analysis</subject><subject>Female</subject><subject>Genes, Immunoglobulin - genetics</subject><subject>Germinal center differentiation</subject><subject>Humans</subject><subject>Immunoglobulin Variable Region - genetics</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - genetics</subject><subject>Male</subject><subject>Membrane Glycoproteins</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Prognosis</subject><subject>Time Factors</subject><issn>1526-9655</issn><issn>2331-4486</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1v1DAQhi0EotvClSPyiVuCHdv5OJYUuiulUKkVV8vrTHYNib3YTtH-HX5pHe0iTpzG0jzzaMYvQu8oyVlNy49td5cXhPDc5oQ2L9CqYIxmnNflS7SioiizphTiAl2G8IOQomSUvUYXVHDBmqJeoT93c1TROKtG_JBec8BuwJvd9zW-BQsBt84GEyLYiH-buMfXNpod2OzGmyew-AFG0Ms83s4Rf3UR34PXC500f90Br1XA997trAvRaLyZDkpHbCz-lLUwjrjde2dToztOh73TxwXqYP4Jk1Fv0KtBjQHenusVevzy-bFdZ92320173WWacRIzzUvKYVs1rBHbuqwq0gxa1QJ0IfqhSj1FKsEGUhcDLWjPtOaNJpQOA2GiYVfow0l78O7XDCHKyQSdllMW3BxkWTYF57ROYH4CtXcheBjkwZtJ-aOkRC6hyBSKXEKRVqZQ0sD7s3neTtD_w88pJKA-AZDOezLgZdAGrIbe-PS7snfmf-5nil-cmQ</recordid><startdate>20040901</startdate><enddate>20040901</enddate><creator>Degan, Massimo</creator><creator>Rupolo, Maurizio</creator><creator>Dal Bo, Michele</creator><creator>Stefanon, Anna</creator><creator>Bomben, Riccardo</creator><creator>Zucchetto, Antonella</creator><creator>Canton, Enrica</creator><creator>Berretta, Massimiliano</creator><creator>Nanni, Paola</creator><creator>Steffan, Agostino</creator><creator>Ferruccio Ballerini, Pier</creator><creator>Damiani, Daniela</creator><creator>Pucillo, Carlo</creator><creator>Attadia, Vincenza</creator><creator>Colombatti, Alfonso</creator><creator>Gattei, Valter</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20040901</creationdate><title>Mutational Status of IgVH Genes Consistent with Antigen-Driven Selection but Not Percent of Mutations Has Prognostic Impact in B-Cell Chronic Lymphocytic Leukemia</title><author>Degan, Massimo ; 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| ispartof | Clinical lymphoma, 2004-09, Vol.5 (2), p.123-126 |
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| subjects | ADP-ribosyl Cyclase - genetics ADP-ribosyl Cyclase 1 Adult Aged Aged, 80 and over Antigens - chemistry Antigens, CD - genetics CD38 expression Cell Differentiation Complementary determining regions DNA Mutational Analysis Female Genes, Immunoglobulin - genetics Germinal center differentiation Humans Immunoglobulin Variable Region - genetics Leukemia, Lymphocytic, Chronic, B-Cell - genetics Male Membrane Glycoproteins Middle Aged Mutation Prognosis Time Factors |
| title | Mutational Status of IgVH Genes Consistent with Antigen-Driven Selection but Not Percent of Mutations Has Prognostic Impact in B-Cell Chronic Lymphocytic Leukemia |
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