Mutational Status, Not Percentage, Has Prognostic Impact in CLL

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Clin Lymphoma. 2004 Sep;5(2):123-6.

Mutational Status of IgVH Genes Consistent with Antigen-Driven

Selection but Not Percent of Mutations Has Prognostic Impact in B-

Cell Chronic Lymphocytic Leukemia.

Degan M, Rupolo M, Bo MD, Stefanon A, Bomben R, Zucchetto A, Canton

E, Berretta M, Nanni P, Steffan A, Ballerini PF, Damiani D, Pucillo

C, Attadia V, Colombatti A, Gattei V.

Clinical and Experimental Hematology Research Unit, Centro di

Riferimento Oncologico, I.R.C.C.S., Aviano, Italy.

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.

PMID: 15453928 [PubMed - in process]