Mutational status of IgVH genes consistent with antigen-driven selection but not percent of mutations has prognostic impact in B-cell chronic lymphocytic leukemia

Massimo Degan, Maurizio Rupolo, Michele Dal Bo, Anna Stefanon, Riccardo Bomben, Antonella Zucchetto, Enrica Canton, Massimiliano Berretta, Paola Nanni, Agostino Steffan, Pier Ferruccio Ballerini, Daniela Damiani, Carlo Pucillo, Vincenza Attadia, Alfonso Colombatti, Valter Gattei

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)123-126
Number of pages4
JournalClinical Lymphoma
Volume5
Issue number2
Publication statusPublished - Sep 2004

Keywords

  • CD38 expression
  • Complementary determining regions
  • Germinal center differentiation

ASJC Scopus subject areas

  • Cancer Research

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    Degan, M., Rupolo, M., Dal Bo, M., Stefanon, A., Bomben, R., Zucchetto, A., Canton, E., Berretta, M., Nanni, P., Steffan, A., Ballerini, P. F., Damiani, D., Pucillo, C., Attadia, V., Colombatti, A., & Gattei, V. (2004). Mutational status of IgVH genes consistent with antigen-driven selection but not percent of mutations has prognostic impact in B-cell chronic lymphocytic leukemia. Clinical Lymphoma, 5(2), 123-126.